Lijun Yan, Vladimir Majerciak, Zhi-Ming Zheng and Ke Lan. Towards Better Understanding of KSHV Life Cycle: from Transcription and Posttranscriptional Regulations to Pathogenesis[J]. Virologica Sinica, 2019, 34(2): 135-161. doi: 10.1007/s12250-019-00114-3
Citation: Lijun Yan, Vladimir Majerciak, Zhi-Ming Zheng, Ke Lan. Towards Better Understanding of KSHV Life Cycle: from Transcription and Posttranscriptional Regulations to Pathogenesis .VIROLOGICA SINICA, 2019, 34(2) : 135-161.  http://dx.doi.org/10.1007/s12250-019-00114-3

卡波氏肉瘤相关疱疹病毒生活周期:转录和转录后调控及致瘤机制

cstr: 32224.14.s12250-019-00114-3
  • 通讯作者: 郑志明, zhengt@exchange.nih.gov, ORCID: 0000-0001-5547-7912
    ; 蓝柯, klan@whu.edu.cn, ORCID: 0000-0002-0384-8598
  • 收稿日期: 2018-11-29
    录用日期: 2019-03-14
    出版日期: 2019-04-25
  • 卡波氏肉瘤相关疱疹病毒是一种重要的人类肿瘤病毒,在其生活周期中表现出潜伏感染和裂解复制两相生命周期。除了引发典型的卡波氏肉瘤之外,该病毒还会引发多中心性卡斯特曼疾病以及原发性渗出性淋巴瘤。卡波氏肉瘤同时也是艾滋病患者中常见的肿瘤之一。在病毒与宿主长期进化和共存的过程中,病毒利用宿主的系统来发展生命周期并不断进化出各种策略以拮抗宿主内的免疫系统从而最终导致肿瘤的发生。因此,更好地了解病毒两相生命周期及其调控的相关机制对我们揭示该病毒致瘤过程是十分有必要的。

Towards Better Understanding of KSHV Life Cycle: from Transcription and Posttranscriptional Regulations to Pathogenesis

  • Corresponding author: Zhi-Ming Zheng, zhengt@exchange.nih.gov Ke Lan, klan@whu.edu.cn
  • ORCID: 0000-0001-5547-7912; 0000-0002-0384-8598
  • Received Date: 29 November 2018
    Accepted Date: 14 March 2019
    Published Date: 25 April 2019
  • Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8 (HHV-8), is etiologically linked to the development of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. These malignancies often occur in immunosuppressed individuals, making KSHV infection-associated diseases an increasing global health concern with persistence of the AIDS epidemic. KSHV exhibits biphasic life cycles between latent and lytic infection and extensive transcriptional and posttranscriptional regulation of gene expression. As a member of the herpesvirus family, KSHV has evolved many strategies to evade the host immune response, which help the virus establish a successful lifelong infection. In this review, we summarize the current research status on the biology of latent and lytic viral infection, the regulation of viral life cycles and the related pathogenesis.

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    1. Abend JR, Uldrick T, Ziegelbauer JM (2010) Regulation of tumor necrosis factor-like weak inducer of apoptosis receptor protein (TWEAKR) expression by Kaposi's sarcoma-associated herpesvirus microRNA prevents TWEAK-induced apoptosis and inflammatory cytokine expression. J Virol 84:12139-12151
        doi: 10.1128/JVI.00884-10

    2. Abend JR, Ramalingam D, Kieffer-Kwon P, Uldrick TS, Yarchoan R, Ziegelbauer JM (2012) Kaposi's sarcoma-associated herpesvirus microRNAs target IRAK1 and MYD88, two components of the toll-like receptor/interleukin-1R signaling cascade, to reduce inflammatory-cytokine expression. J Virol 86:11663-11674
        doi: 10.1128/JVI.01147-12

    3. Adams V, Kempf W, Hassam S, Briner J, Schmid M, Moos R, Pfaltz M (1995) Detection of several types of human papilloma viruses in AIDS-associated Kaposi's sarcoma. J Med Virol 46:189-193
        doi: 10.1002/(ISSN)1096-9071

    4. Ajiro M, Zheng ZM (2014) Oncogenes and RNA splicing of human tumor viruses. Emerg Microbes Infect 3:e63

    5. Akula SM, Pramod NP, Wang FZ, Chandran B (2001) Human herpesvirus 8 envelope-associated glycoprotein B interacts with heparan sulfate-like moieties. Virology 284:235-249
        doi: 10.1006/viro.2001.0921

    6. Akula SM, Pramod NP, Wang F, Chandran B (2002) Integrin α3/β1 (CD 49c/29) is a cellular receptor for Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) entry into the target cells. Cell 108:407-419
        doi: 10.1016/S0092-8674(02)00628-1

    7. Al-Kzayer LF, Keizer P, Abdulraheem FT, Sano K, Kamata M, Sakashita K, Habbaba LA, Koike K (2016) Rapidly progressive Kaposi's Sarcoma in an Iraqi boy received valproic acid: a case report and review of literature. BMC Pediatr 16:111
        doi: 10.1186/s12887-016-0653-3

    8. Ameres SL, Zamore PD (2013) Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol 14:475-488
        doi: 10.1038/nrm3611

    9. Andrei G, Snoeck R (2015) Kaposi's sarcoma-associated herpesvirus: the role of lytic replication in targeted therapy. Curr Opin Infect Dis 28:611-624
        doi: 10.1097/QCO.0000000000000213

    10. Areste C, Blackbourn DJ (2009) Modulation of the immune system by Kaposi's sarcoma-associated herpesvirus. Trends Microbiol 17:119-129
        doi: 10.1016/j.tim.2008.12.001

    11. Arias C, Welsberd B, Stern-Ginossar N, Mercier A, Madrid AS, Bellare P, Holdorf M, Weissman JS, Ganem D (2014) KSHV 2.0: a comprehensive annotation of the Kaposi's sarcoma-associated herpesvirus genome using next-generation sequencing reveals novel genomic and functional features. PLoS Pathog 10:e1003847
        doi: 10.1371/journal.ppat.1003847

    12. Asou H, Said JW, Yang R, Munker R, Park DJ, Kamada N, Koeffler HP (1998) Mechanisms of growth control of Kaposi's sarcoma-associated herpes virus-associated primary effusion lymphoma cells. Blood 91:2475-2481

    13. Avitabile E, Forghieri C, Campadelli-Fiume G (2009) Cross talk among the glycoproteins involved in herpes simplex virus entry and fusion: the interaction between gB and gH/gL does not necessarily require gD. J Virol 83:10752-10760
        doi: 10.1128/JVI.01287-09

    14. Baghian A, Luftig M, Black JB, Meng YX, Pau CP, Voss T, Pellett PE, Kousoulas KG (2000) Glycoprotein B of human herpesvirus 8 is a component of the virion in a cleaved form composed of amino- and carboxyl-terminal fragments. Virology 269:18-25
        doi: 10.1006/viro.2000.0198

    15. Bagneris C, Ageichik AV, Cronin N, Wallace B, Collins M, Boshoff C, Waksman G, Barrett T (2008) Crystal structure of a vFlip-IKKgamma complex: insights into viral activation of the IKK signalosome. Mol Cell 30:620-631
        doi: 10.1016/j.molcel.2008.04.029

    16. Bajaj BG, Verma SC, Lan K, Cotter MA, Woodman ZL, Robertson ES (2006) KSHV encoded LANA upregulates Pim-1 and is a substrate for its kinase activity. Virology 351:18-28
        doi: 10.1016/j.virol.2006.03.037

    17. Ballestas ME, Kaye KM (2001) Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 mediates episome persistence through cis-acting terminal repeat (TR) sequence and specifically binds TR DNA. J Virol 75:3250-3258
        doi: 10.1128/JVI.75.7.3250-3258.2001

    18. Ballestas ME, Chatis PA, Kaye KM (1999) Efficient persistence of extrachromosomal KSHV DNA mediated by latency-associated nuclear antigen. Science 284:641-644
        doi: 10.1126/science.284.5414.641

    19. Baresova P, Pitha PM, Lubyova B (2013) Distinct roles of Kaposi's sarcoma-associated herpesvirus-encoded viral interferon regulatory factors in inflammatory response and cancer. J Virol 87:9398-9410
        doi: 10.1128/JVI.03315-12

    20. Bechtel JT, Winant RC, Ganem D (2005) Host and viral proteins in the virion of Kaposi's sarcoma-associated herpesvirus. J Virol 79:4952-4964
        doi: 10.1128/JVI.79.8.4952-4964.2005

    21. Bellare P, Ganem D (2009) Regulation of KSHV lytic switch protein expression by a virus-encoded microRNA: an evolutionary adaptation that fine-tunes lytic reactivation. Cell Host Microbe 6:570-575
        doi: 10.1016/j.chom.2009.11.008

    22. Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagschal A, Feil R, Schreiber SL, Lander ES (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125:315-326
        doi: 10.1016/j.cell.2006.02.041

    23. Bieleski L, Talbot SJ (2001) Kaposi's sarcoma-associated herpesvirus vCyclin open reading frame contains an internal ribosome entry site. J Virol 75:1864-1869
        doi: 10.1128/JVI.75.4.1864-1869.2001

    24. Boldogh I, Szaniszlo P, Bresnahan WA, Flaitz CM, Nichols MC, Albrecht T (1996) Kaposi's sarcoma herpesvirus-like DNA sequences in the saliva of individuals infected with human immunodeficiency virus. Clin Infect Dis 23:406-407
        doi: 10.1093/clinids/23.2.406

    25. Boshoff C (2002) Kaposi's Sarcoma Biology. IUBMB Life 53:259-261
        doi: 10.1080/15216540212645

    26. Botto S, Totonchy JE, Gustin JK, Moses AV (2015) Kaposi sarcoma herpesvirus induces HO-1 during de novo infection of endothelial cells via viral miRNA-dependent and -independent mechanisms. MBio 6:e00668

    27. Boyne JR, Colgan KJ, Whitehouse A (2008) Recruitment of the complete hTREX complex is required for Kaposi's sarcoma-associated herpesvirus intronless mRNA nuclear export and virus replication. PLoS Pathog 4:e1000194
        doi: 10.1371/journal.ppat.1000194

    28. Brulois KF, Chang H, Lee AS, Ensser A, Wong LY, Toth Z, Lee SH, Lee HR, Myoung J, Ganem D, Oh TK, Kim JF, Gao SJ, Jung JU (2012) Construction and manipulation of a new Kaposi's sarcoma-associated herpesvirus bacterial artificial chromosome clone. J Virol 86:9708-9720
        doi: 10.1128/JVI.01019-12

    29. Brulois K, Toth Z, Wong LY, Feng P, Gao SJ, Ensser A, Jung JU (2014) Kaposi's sarcoma-associated herpesvirus K3 and K5 ubiquitin E3 ligases have stage-specific immune evasion roles during lytic replication. J Virol 88:9335-9349
        doi: 10.1128/JVI.00873-14

    30. Bu W, Palmeri D, Krishnan R, Marin R, Aris VM, Soteropoulos P, Lukac DM (2008) Identification of direct transcriptional targets of the Kaposi's sarcoma-associated herpesvirus Rta lytic switch protein by conditional nuclear localization. J Virol 82:10709-10723
        doi: 10.1128/JVI.01012-08

    31. Byun H, Gwack Y, Hwang S, Choe J (2002) Kaposi's Sarcoma-associated herpesvirus open reading frame (ORF) 50 transactivates K8 and ORF57 promoters via heterogeneous response elements. Mol Cells 14:185-191

    32. Cai X, Cullen BR (2006) Transcriptional origin of Kaposi's sarcoma-associated herpesvirus microRNAs. J Virol 80:2234-2242
        doi: 10.1128/JVI.80.5.2234-2242.2006

    33. Cai X, Lu S, Zhang Z, Gonzalez CM, Damania B, Cullen BR (2005) Kaposi's sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells. Proc Natl Acad Sci USA 102:5570-5575
        doi: 10.1073/pnas.0408192102

    34. Cai Q, Knight JS, Verma SC, Zald P, Robertson ES (2006) EC5S ubiquitin complex is recruited by KSHV latent antigen LANA for degradation of the VHL and p53 tumor suppressors. PLoS Pathog 2:1002-1012

    35. Cai Q, Verma SC, Lu J, Robertson ES (2010) Molecular biology of Kaposi's sarcoma-associated herpesvirus and related oncogenesis. Adv Virus Res 78:87-142
        doi: 10.1016/B978-0-12-385032-4.00003-3

    36. Campbell M, Izumiya Y (2012) Post-translational modifications of Kaposi's sarcoma-associated herpesvirus regulatory proteins-SUMO and KSHV. Front Microbiol 3:31

    37. Campbell M, Chang PC, Huerta S, Izumiya C, Davis R, Tepper CG, Kim KY, Shevchenko B, Wang DH, Jung JU, Luciw PA, Kung HJ, Izumiya Y (2012) Protein arginine methyltransferase 1-directed methylation of Kaposi sarcoma-associated herpesvirus latency-associated nuclear antigen. J Biol Chem 287:5806-5818
        doi: 10.1074/jbc.M111.289496

    38. Cao Y, Minhas V, Tan X, Huang J, Wang B, Zhu M, Gao Y, Zhao T, Yang L, Wood C (2014) High prevalence of early childhood infection by Kaposi's sarcoma-associated herpesvirus in a minority population in China. Clin Microbiol Infect 20:475-481
        doi: 10.1111/1469-0691.12340

    39. Carroll KD, Khadim F, Spadavecchia S, Palmeri D, Lukac DM (2007) Direct interactions of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 ORF50/Rta protein with the cellular protein octamer-1 and DNA are critical for specifying transactivation of a delayed-early promoter and stimulating viral reactivation. J Virol 81:8451-8467
        doi: 10.1128/JVI.00265-07

    40. Chandriani S, Ganem D (2010) Array-based transcript profiling and limiting-dilution reverse transcription-PCR analysis identify additional latent genes in Kaposi's sarcoma-associated herpesvirus. J Virol 84:5565-5573
        doi: 10.1128/JVI.02723-09

    41. Chang PC, Li M (2008) Kaposi's sarcoma-associated herpesvirus K-cyclin interacts with Cdk9 and stimulates Cdk9-mediated phosphorylation of p53 tumor suppressor. J Virol 82:278-290
        doi: 10.1128/JVI.01552-07

    42. Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS (1994) Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 266:1865-1869
        doi: 10.1126/science.7997879

    43. Chang H, Wachtman LM, Pearson CB, Lee JS, Lee HR, Lee SH, Vieira J, Mansfield KG, Jung JU (2009) Non-human primate model of Kaposi's sarcoma-associated herpesvirus infection. PLoS Pathog 5:e1000606
        doi: 10.1371/journal.ppat.1000606

    44. Chang HC, Hsieh TH, Lee YW, Tsai CF, Tsai YN, Cheng CC, Wang HW (2016) c-Myc and viral cofactor Kaposin B co-operate to elicit angiogenesis through modulating miRNome traits of endothelial cells. BMC Syst Biol 10(Suppl 1):1

    45. Chaudhary PM, Jasmin A, Eby MT, Hood L (1999) Modulation of the NF-κB pathway by virally encoded death effector domains-containing proteins. Oncogene 18:5738-5746
        doi: 10.1038/sj.onc.1202976

    46. Chen J, Ueda K, Sakakibara S, Okuno T, Parravicini C, Corbellino M, Yamanishi K (2001) Activation of latent Kaposi's sarcoma-associated herpesvirus by demethylation of the promoter of the lytic transactivator. Proc Natl Acad Sci USA 98:4119-4124
        doi: 10.1073/pnas.051004198

    47. Chen J, Ye F, Xie J, Kuhne K, Gao SJ (2009) Genome-wide identification of binding sites for Kaposi's sarcoma-associated herpesvirus lytic switch protein, RTA. Virology 386:290-302
        doi: 10.1016/j.virol.2009.01.031

    48. Chen HS, Wikramasinghe P, Showe L, Lieberman PM (2012) Cohesins repress Kaposi's sarcoma-associated herpesvirus immediate early gene transcription during latency. J Virol 86:9454-9464
        doi: 10.1128/JVI.00787-12

    49. Chen HS, Lu F, Lieberman PM (2013) Epigenetic regulation of EBV and KSHV latency. Curr Opin Virol 3:251-259
        doi: 10.1016/j.coviro.2013.03.004

    50. Cheng F, Weidner-Glunde M, Varjosalo M, Rainio EM, Lehtonen A, Schulz TF, Koskinen PJ, Taipale J, Ojala PM (2009) KSHV reactivation from latency requires Pim-1 and Pim-3 kinases to inactivate the latency-associated nuclear antigen LANA. PLoS Pathog 5:e1000324
        doi: 10.1371/journal.ppat.1000324

    51. Chugh PE, Sin SH, Ozgur S, Henry DH, Menezes P, Griffith J, Eron JJ, Damania B, Dittmer DP (2013) Systemically circulating viral and tumor-derived microRNAs in KSHV-associated malignancies. PLoS Pathog 9:e1003484
        doi: 10.1371/journal.ppat.1003484

    52. Cianfrocca M, Cooley TP, Lee JY, Rudek MA, Scadden DT, Ratner L, Pluda JM, Figg WD, Krown SE, Dezube BJ (2002) Matrix metalloproteinase inhibitor COL-3 in the treatment of AIDS-related Kaposi's sarcoma: a phase I AIDS malignancy consortium study. J Clin Oncol 20:153-159

    53. Cook-Mozaffari P, Newton R, Beral V, Burkitt DP (1998) The geographical distribution of Kaposi's sarcoma and of lymphomas in Africa before the AIDS epidemic. Br J Cancer 78:1521-1528
        doi: 10.1038/bjc.1998.717

    54. Corcoran JA, McCormick C (2015) Viral activation of stress-regulated Rho-GTPase signaling pathway disrupts sites of mRNA degradation to influence cellular gene expression. Small GTPases 6:178-185
        doi: 10.1080/21541248.2015.1093068

    55. Coscoy L (2007) Immune evasion by Kaposi's sarcoma-associated herpesvirus. Nat Rev Immunol 7:391-401
        doi: 10.1038/nri2076

    56. Cousins E, Nicholas J (2013) Role of human herpesvirus 8 interleukin-6-activated gp130 signal transducer in primary effusion lymphoma cell growth and viability. J Virol 87:10816-10827
        doi: 10.1128/JVI.02047-13

    57. Dai L, Qiao J, Nguyen D, Struckhoff AP, Doyle L, Bonstaff K, Valle LD, Parsons C, Toole BP, Renne R, Qin Z (2016) Role of heme oxygenase-1 in the pathogenesis and tumorigenicity of Kaposi's sarcoma-associated herpesvirus. Oncotarget 7:10459-10471

    58. Davis DA, Rinderknecht AS, Zoeteweij JP, Aoki Y, Read-Connole EL, Tosato G, Blauvelt A, Yarchoan R (2001) Hypoxia induces lytic replication of Kaposi sarcoma-associated herpesvirus. Blood 97:3244-3250
        doi: 10.1182/blood.V97.10.3244

    59. Davis ZH, Verschueren E, Jang GM, Kleffman K, Johnson JR, Park J, Von Dollen J, Maher MC, Johnson T, Newton W, Jager S, Shales M, Horner J, Hernandez RD, Krogan NJ, Glaunsinger BA (2015) Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes. Mol Cell 57:349-360
        doi: 10.1016/j.molcel.2014.11.026

    60. De Leon Vazquez E, Kaye KM (2011) The internal Kaposi's sarcoma-associated herpesvirus LANA regions exert a critical role on episome persistence. J Virol 85:7622-7633
        doi: 10.1128/JVI.00304-11

    61. Deng H, Young A, Sun R (2000) Auto-activation of the rta gene of human herpesvirus-8/Kaposi's sarcoma-associated herpesvirus. J Gen Virol 81:3043-3048
        doi: 10.1099/0022-1317-81-12-3043

    62. Deng Z, Wang Z, Lieberman PM (2012) Telomeres and viruses: common themes of genome maintenance. Front Oncol 2:201

    63. Dimaio TA, Lagunoff M (2012) KSHV induction of angiogenic and lymphangiogenic phenotypes. Front Microbiol 3:102

    64. Dittmer DP, Damania B (2016) Kaposi sarcoma-associated herpesvirus: immunobiology, oncogenesis, and therapy. J Clin Invest 126:3165-3175
        doi: 10.1172/JCI84418

    65. Dittmer D, Lagunoff M, Renne R, Staskus KA, Haase A, Ganem D (1998) A cluster of latently expressed genes in Kaposi's Sarcoma-associated herpesvirus. J Virol 72:8309-8315

    66. Dollard SC, Nelson KE, Ness PM, Stambolis V, Kuehnert MJ, Pellett PE, Cannon MJ (2005) Possible transmission of human herpesvirus-8 by blood transfusion in a historical United States cohort. Transfusion 45:500-503
        doi: 10.1111/trf.2005.45.issue-4

    67. Dollard SC, Butler LM, Jones AM, Mermin JH, Chidzonga M, Chipato T, Shiboski CH, Brander C, Mosam A, Kiepiela P, Hladik W, Martin JN (2010) Substantial regional differences in human herpesvirus 8 seroprevalence in sub-Saharan Africa: insights on the origin of the "Kaposi's sarcoma belt". Int J Cancer 127:2395-2401
        doi: 10.1002/ijc.25235

    68. Dorsett D (2011) Cohesin: genomic insights into controlling gene transcription and development. Curr Opin Genet Dev 21:199-206
        doi: 10.1016/j.gde.2011.01.018

    69. Dourmishev LA, Dourmishev AL, Palmeri D, Schwartz RA, Lukac DM (2003) Molecular genetics of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) epidemiology and pathogenesis. Microbiol Mol Biol Rev 67:175-212
        doi: 10.1128/MMBR.67.2.175-212.2003

    70. Duan W, Wang S, Liu S, Wood C (2001) Characterization of Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8 ORF57 promoter. Arch Virol 146:403-413
        doi: 10.1007/s007050170185

    71. Dupin N, Fisher C, Kellam P, Ariad S, Tulliez M, Franck N, Marck EV, Salmon D, Gorin I, Escande JP, Weiss RA, Alitalo K, Boshoff C (1999) Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma. Proc Natl Acad Sci USA 96:4546-4551
        doi: 10.1073/pnas.96.8.4546

    72. Ellison TJ, Izumiya Y, Izumiya C, Luciw PA, Kung HJ (2009) A comprehensive analysis of recruitment and transactivation potential of K-Rta and K-bZIP during reactivation of Kaposi's sarcoma-associated herpesvirus. Virology 387:76-88
        doi: 10.1016/j.virol.2009.02.016

    73. Eltom MA, Mbulaiteye SM, Dada AJ, Whitby D, Biggar RJ (2002) Transmission of human herpesvirus 8 by sexual activity among adults in Lagos, Nigeria. AIDS 16:2473-2478
        doi: 10.1097/00002030-200212060-00014

    74. Fakhari FD, Dittmer DP (2002) Charting latency transcripts in Kaposi's sarcoma-associated herpesvirus by whole-genome real-time quantitative PCR. J Virol 76:6213-6223
        doi: 10.1128/JVI.76.12.6213-6223.2002

    75. Fatahzadeh M (2012) Kaposi sarcoma: review and medical management update. Oral Surg Oral Med Oral Pathol Oral Radiol 113:2-16
        doi: 10.1016/j.tripleo.2011.05.011

    76. Field N, Low W, Daniels M, Howell S, Daviet L, Boshoff C, Collins M (2003) KSHV vFLIP binds to IKK-γ to activate IKK. J Cell Sci 116:3721-3728
        doi: 10.1242/jcs.00691

    77. Flore O, Raffi S, Ely S, O'Leary JJ, Hyjek EM, Cesarman E (1998) Transformation of primary human endothelial cells by Kaposi's sarcoma-associated herpesvirus. Nature 394:588-592
        doi: 10.1038/29093

    78. Ford PW, Bryan BA, Dyson OF, Weidner DA, Chintalgattu V, Akula SM (2006) Raf/MEK/ERK signalling triggers reactivation of Kaposi's sarcoma-associated herpesvirus latency. J Gen Virol 87:1139-1144
        doi: 10.1099/vir.0.81628-0

    79. Forte E, Raja AN, Shamulailatpam P, Manzano M, Schipma MJ, Casey JL, Gottwein E (2015) MicroRNA-mediated transformation by the Kaposi's sarcoma-associated herpesvirus Kaposin locus. J Virol 89:2333-2341
        doi: 10.1128/JVI.03317-14

    80. Fu B, Sun F, Li B, Yang L, Zeng Y, Sun X, Xu F, Rayner S, Guadalupe M, Gao SJ, Wang L (2009) Seroprevalence of Kaposi's sarcoma-associated herpesvirus and risk factors in Xinjiang, China. J Med Virol 81:1422-1431
        doi: 10.1002/jmv.v81:8

    81. Fujimuro M, Liu J, Zhu J, Yokosawa H, Hayward SD (2005) Regulation of the interaction between glycogen synthase kinase 3 and the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen. J Virol 79:10429-10441
        doi: 10.1128/JVI.79.16.10429-10441.2005

    82. Full F, Jungick D, Reuter N, Bogner E, Brulois K, Scholz B, Sturzl M, Myoung J, Jung JU, Stamminger T, Ensser A (2014) Kaposi's sarcoma associated herpesvirus tegument protein ORF75 is essential for viral lytic replication and plays a critical role in the antagonization of ND10-Instituted intrinsic immunity. PLoS Pathog 10:e1003863
        doi: 10.1371/journal.ppat.1003863

    83. Ganem D (1997) KSHV and Kaposi's Sarcoma: the end of the beginning? Cell 91:157-160
        doi: 10.1016/S0092-8674(00)80398-0

    84. Ganem D (2010) KSHV and the pathogenesis of Kaposi sarcoma: listening to human biology and medicine. J Clin Invest 120:939-949
        doi: 10.1172/JCI40567

    85. Gao SJ, Kingsley L, Li M, Zheng W, Parravicini C, Ziegler J, Newton R, Rinaldo CR, Saah A, Phair J, Detels R, Chang Y, Moore PS (1996) KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma. Nat Med 2:925-928
        doi: 10.1038/nm0896-925

    86. Garber AC, Shu MA, Hu J, Renne R (2001) DNA binding and modulation of gene expression by the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus. J Virol 75:7882-7892
        doi: 10.1128/JVI.75.17.7882-7892.2001

    87. Giffin L, Damania B (2014) KSHV: pathways to tumorigenesis and persistent infection. Adv Virus Res 88:111-159
        doi: 10.1016/B978-0-12-800098-4.00002-7

    88. Gillen J, Li W, Liang Q, Avey D, Wu J, Wu F, Myoung J, Zhu F (2015) A survey of the interactome of Kaposi's sarcoma-associated herpesvirus ORF45 revealed its binding to viral ORF33 and cellular USP7, resulting in stabilization of ORF33 that is required for production of progeny viruses. J Virol 89:4918-4931
        doi: 10.1128/JVI.02925-14

    89. Godden-Kent D, Talbot SJ, Boshoff C, Chang Y, Moore P, Weiss RA, Mittnacht S (1997) The cyclin encoded by Kaposi's sarcoma-associated herpesvirus stimulates cdk6 To phosphorylate the retinoblastoma protein and histone H1. J Virol 71:4193-4198

    90. Gottwein E, Cai X, Cullen BR (2006) Expression and function of microRNAs encoded by Kaposi's sarcoma-associated herpesvirus. Cold Spring Harb Symp Quant Biol 71:357-364
        doi: 10.1101/sqb.2006.71.004

    91. Gottwein E, Mukherjee N, Sachse C, Frenzel C, Majoros WH, Chi JT, Braich R, Manoharan M, Soutschek J, Ohler U, Cullen BR (2007) A viral microRNA functions as an orthologue of cellular miR-155. Nature 450:1096-1099
        doi: 10.1038/nature05992

    92. Gottwein E, Corcoran DL, Mukherjee N, Skalsky RL, Hafner M, Nusbaum JD, Shamulailatpam P, Love CL, Dave SS, Tuschl T, Ohler U, Cullen BR (2011) Viral microRNA targetome of KSHV-infected primary effusion lymphoma cell lines. Cell Host Microbe 10:515-526
        doi: 10.1016/j.chom.2011.09.012

    93. Gradoville L, Gerlach J, Grogan E, Shedd D, Nikiforow S, Metroka C, Miller G (2000) Kaposi's sarcoma-associated herpesvirus open reading frame 50/Rta protein activates the entire viral lytic cycle in the HH-B2 primary effusion lymphoma cell line. J Virol 74:6207-6212
        doi: 10.1128/JVI.74.13.6207-6212.2000

    94. Graham C, Matta H, Yang Y, Yi H, Suo Y, Tolani B, Chaudhary PM (2013) Kaposi's sarcoma-associated herpesvirus oncoprotein K13 protects against B cell receptor-induced growth arrest and apoptosis through NF-kappaB activation. J Virol 87:2242-2252
        doi: 10.1128/JVI.01393-12

    95. Gregory SM, West JA, Dillon PJ, Hilscher C, Dittmer DP, Damania B (2009) Toll-like receptor signaling controls reactivation of KSHV from latency. Proc Natl Acad Sci USA 106:11725-11730
        doi: 10.1073/pnas.0905316106

    96. Gregory SM, Davis BK, West JA, Taxman DJ, Matsuzawa S, Reed JC, Ting JP, Damania B (2011) Discovery of a viral NLR homolog that inhibits the inflammasome. Science 331:330-334
        doi: 10.1126/science.1199478

    97. Griffiths R, Whitehouse A (2007) Herpesvirus saimiri episomal persistence is maintained via interaction between open reading frame 73 and the cellular chromosome-associated protein MeCP2. J Virol 81:4021-4032
        doi: 10.1128/JVI.02171-06

    98. Grossmann C, Podgrabinska S, Skobe M, Ganem D (2006) Activation of NF-kappaB by the latent vFLIP gene of Kaposi's sarcoma-associated herpesvirus is required for the spindle shape of virus-infected endothelial cells and contributes to their proinflammatory phenotype. J Virol 80:7179-7185
        doi: 10.1128/JVI.01603-05

    99. Grundhoff A, Sullivan CS, Ganem D (2006) A combined computational and microarray-based approach identifies novel microRNAs encoded by human gamma-herpesviruses. RNA 12:733-750
        doi: 10.1261/rna.2326106

    100. Guasparri I, Keller SA, Cesarman E (2004) KSHV vFLIP is essential for the survival of infected lymphoma cells. J Exp Med 199:993-1003
        doi: 10.1084/jem.20031467

    101. Gunther T, Grundhoff A (2010) The epigenetic landscape of latent Kaposi sarcoma-associated herpesvirus genomes. PLoS Pathog 6:e1000935
        doi: 10.1371/journal.ppat.1000935

    102. Haas DA, Bala K, Busche G, Weidner-Glunde M, Santag S, Kati S, Gramolelli S, Damas M, Dittrich-Breiholz O, Kracht M, Ruckert J, Varga Z, Keri G, Schulz TF (2013) The inflammatory kinase MAP4K4 promotes reactivation of Kaposi's sarcoma herpesvirus and enhances the invasiveness of infected endothelial cells. PLoS Pathog 9:e1003737
        doi: 10.1371/journal.ppat.1003737

    103. Haddad L, El Hajj H, Abou-Merhi R, Kfoury Y, Mahieux R, El-Sabban M, Bazarbachi A (2008) KSHV-transformed primary effusion lymphoma cells induce a VEGF-dependent angiogenesis and establish functional gap junctions with endothelial cells. Leukemia 22:826-834
        doi: 10.1038/sj.leu.2405081

    104. Hahn AS, Kaufmann JK, Wies E, Naschberger E, Panteleev-Ivlev J, Schmidt K, Holzer A, Schmidt M, Chen J, Konig S, Ensser A, Myoung J, Brockmeyer NH, Sturzl M, Fleckenstein B, Neipel F (2012) The ephrin receptor tyrosine kinase A2 is a cellular receptor for Kaposi's sarcoma-associated herpesvirus. Nat Med 18:961-966
        doi: 10.1038/nm.2805

    105. Han Z, Swaminathan S (2006) Kaposi's sarcoma-associated herpesvirus lytic gene ORF57 is essential for infectious virion production. J Virol 80:5251-5260
        doi: 10.1128/JVI.02570-05

    106. Haque M, Davis DA, Wang V, Widmer I, Yarchoan R (2003) Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) contains hypoxia response elements: relevance to lytic Induction by hypoxia. J Virol 77:6761-6768
        doi: 10.1128/JVI.77.12.6761-6768.2003

    107. Hensler HR, Tomaszewski MJ, Rappocciolo G, Rinaldo CR, Jenkins FJ (2014) Human herpesvirus 8 glycoprotein B binds the entry receptor DC-SIGN. Virus Res 190:97-103
        doi: 10.1016/j.virusres.2014.07.003

    108. Herold M, Bartkuhn M, Renkawitz R (2012) CTCF: insights into insulator function during development. Development 139:1045-1057
        doi: 10.1242/dev.065268

    109. Hladik W, Dollard SC, Mermin J, Fowlkes AL, Downing D, Amin MM, Banage F, Nzaro E, Kataaha P, Dondero TJ, Pellett PE, Lackritz EM (2006) Transmission of human herpesvirus 8 by blood transfusion. N Engl J Med 355:1331-1338
        doi: 10.1056/NEJMoa055009

    110. Hladik W, Pellett PE, Hancock J, Downing R, Gao H, Packel L, Mimbe D, Nzaro E, Mermin J (2012) Association between transfusion with human herpesvirus 8 antibody-positive blood and subsequent mortality. J Infect Dis 206:1497-1503
        doi: 10.1093/infdis/jis543

    111. Hu J, Renne R (2005) Characterization of the minimal replicator of Kaposi's sarcoma-associated herpesvirus latent origin. J Virol 79:2637-2642
        doi: 10.1128/JVI.79.4.2637-2642.2005

    112. Hu Z, Usherwood EJ (2014) Immune escape of gamma-herpesviruses from adaptive immunity. Rev Med Virol 24:365-378
        doi: 10.1002/rmv.v24.6

    113. Hu J, Yang Y, Turner PC, Jain V, McIntyre LM, Renne R (2014) LANA binds to multiple active viral and cellular promoters and associates with the H3K4methyltransferase hSET1 complex. PLoS Pathog 10:e1004240
        doi: 10.1371/journal.ppat.1004240

    114. Hu M, Wang C, Li W, Lu W, Bai Z, Qin D, Yan Q, Zhu J, Krueger BJ, Renne R, Gao SJ, Lu C (2015) A KSHV microRNA directly targets G protein-coupled receptor kinase 2 to promote the migration and invasion of endothelial cells by inducing CXCR113 and activating AKT signaling. PLoS Pathog 11:e1005171
        doi: 10.1371/journal.ppat.1005171

    115. Hunte R, Alonso P, Thomas R, Bazile CA, Ramos JC, van der Weyden L, Dominguez-Bendala J, Khan WN, Shembade N (2018) CADM1 is essential for KSHV-encoded vGPCR-and vFLIP-mediated chronic NF-kappaB activation. PLoS Pathog 14:e1006968
        doi: 10.1371/journal.ppat.1006968

    116. Iscovich J, Boffetta P, Winkelmann R, Brennan P, Azizi E (1998) Classic Kaposi's sarcoma in Jews living in Israel. AIDS 12:2067-2072
        doi: 10.1097/00002030-199815000-00019

    117. Ishido S, Wang C, Lee BS, Cohen GB, Jung JU (2000) Downregulation of major histocompatibility complex class I molecules by Kaposi's sarcoma-associated herpesvirus K3 and K5 proteins. J Virol 74:5300-5309
        doi: 10.1128/JVI.74.11.5300-5309.2000

    118. Izumiya Y, Lin SF, Ellison TJ, Levy AM, Mayeur GL, Izumiya C, Kung HJ (2003) Cell cycle regulation by Kaposi's Sarcoma-associated herpesvirus K-bZIP: direct interaction with cyclin-CDK2 and induction of G1 growth arrest. J Virol 77:9652-9661
        doi: 10.1128/JVI.77.17.9652-9661.2003

    119. Jackson BR, Boyne JR, Noerenberg M, Taylor A, Hautbergue GM, Walsh MJ, Wheat R, Blackbourn DJ, Wilson SA, Whitehouse A (2011) An interaction between KSHV ORF57 and UIF provides mRNA-adaptor redundancy in herpesvirus intronless mRNA export. PLoS Pathog 7:e1002138
        doi: 10.1371/journal.ppat.1002138

    120. Jarviluoma A, Koopal S, Rasanen S, Makela TP, Ojala PM (2004) KSHV viral cyclin binds to p27KIP1 in primary effusion lymphomas. Blood 104:3349-3354
        doi: 10.1182/blood-2004-05-1798

    121. Jenner RG, Alba MM, Boshoff C, Kellam P (2001) Kaposi's sarcoma-associated herpesvirus latent and lytic gene expression as revealed by DNA arrays. J Virol 75:891-902
        doi: 10.1128/JVI.75.2.891-902.2001

    122. Jha HC, Lu J, Verma SC, Banerjee S, Mehta D, Robertson ES (2014) Kaposi's sarcoma-associated herpesvirus genome programming during the early stages of primary infection of peripheral blood mononuclear cells. MBio 5:e02261-14

    123. Jones KD, Aoki Y, Chang Y, Moore PS, Yarchoan R, Tosato G (1999) Involvement of Interleukin-10 (IL-10) and viral IL-6 in the spontaneous growth of Kaposi's sarcoma herpesvirus-associated infected primary effusion lymphoma cells. Blood 94:2871-2879

    124. Jones T, Ye F, Bedolla R, Huang Y, Meng J, Qian L, Pan H, Zhou F, Moody R, Wagner B, Arar M, Gao SJ (2012) Direct and efficient cellular transformation of primary rat mesenchymal precursor cells by KSHV. J Clin Invest 122:1076-1081
        doi: 10.1172/JCI58530

    125. Jones T, Ramos da Silva S, Bedolla R, Ye F, Zhou F, Gao SJ (2014) Viral cyclin promotes KSHV-induced cellular transformation and tumorigenesis by overriding contact inhibition. Cell Cycle 13:845-858
        doi: 10.4161/cc.27758

    126. Jr JF, Kong WP, Hottiger MO, Nabel GJ (1999) p53 inhibition by the LANA of KSHV protect against cell death. Nature 402:889-894
        doi: 10.1038/47266

    127. Kakavand-Ghalehnoei R, Shoja Z, Najafi A, Mollahoseini MH, Shahmahmoodi S, Marashi SM, Nejati A, Jalilvand S (2016) Prevalence of human herpesvirus-8 among HIV-infected patients, intravenous drug users and the general population in Iran. Sex Health 13:295-298
        doi: 10.1071/SH15192

    128. Kaleeba JA, Berger EA (2006) Kaposi's sarcoma-associated Herpesvirus fusion-entry receptor: cystine transporter xCT. Science 311:1921-1924
        doi: 10.1126/science.1120878

    129. Kang H, Wiedmer A, Yuan Y, Robertson ES, Lieberman PM (2011) Coordination of KSHV latent and lytic gene control by CTCF-cohesin mediated chromosome conformation. PLoS Pathog 7:e1002140
        doi: 10.1371/journal.ppat.1002140

    130. Kang JG, Majerciak V, Uldrick TS, Wang X, Kruhlak M, Yarchoan R, Zheng ZM (2011a) Kaposi's sarcoma-associated herpesviral IL-6 and human IL-6 open reading frames contain miRNA binding sites and are subject to cellular miRNA regulation. J Pathol 225:378-389
        doi: 10.1002/path.2962

    131. Kang JG, Pripuzova N, Majerciak V, Kruhlak M, Le SY, Zheng ZM (2011b) Kaposi's sarcoma-associated herpesvirus ORF57 promotes escape of viral and human interleukin-6 from microRNA-mediated suppression. J Virol 85:2620-2630
        doi: 10.1128/JVI.02144-10

    132. Kaplan L (2013) Human herpesvirus-8: Kaposi sarcoma, multicentric castleman disease, and primary effusion lymphoma. Hematol Am Soc Hematol Educ Program 2013:103-108
        doi: 10.1182/asheducation-2013.1.103

    133. Kedes DH, Lagunoff M, Renne R, Ganem D (1997) Identification of the gene encoding the major latency-associated nuclear antigen of the Kaposi's Sarcoma-associated Herpesvirus. J Clin Investig 100:2606-2610
        doi: 10.1172/JCI119804

    134. Kelley-Clarke B, De Leon-Vazquez E, Slain K, Barbera AJ, Kaye KM (2009) Role of Kaposi's sarcoma-associated herpesvirus C-terminal LANA chromosome binding in episome persistence. J Virol 83:4326-4337
        doi: 10.1128/JVI.02395-08

    135. Kieffer-Kwon P, Happel C, Uldrick TS, Ramalingam D, Ziegelbauer JM (2015) KSHV microRNAs repress tropomyosin 1 and increase anchorage-independent growth and endothelial tube formation. PLoS ONE 10:e0135560
        doi: 10.1371/journal.pone.0135560

    136. Kieshner JR, Lukac DM, Chang J, Ganem D (2000) Kaposi's sarcoma-associated herpesvirus open reading frame 57 encodes a posttranscriptional regulator with multiple distinct activities. J Virol 74:3586-3597
        doi: 10.1128/JVI.74.8.3586-3597.2000

    137. Kliche S, Nagel W, Kremmer E, Atzler C, Ege A, Knorr T, Koszinowski U, Kolanus W, Haas J (2001) Signaling by human herpesvirus 8 kaposin A through direct membrane recruitment of cytohesin-1. Mol Cells 7:833-843
        doi: 10.1016/S1097-2765(01)00227-1

    138. Ko YC, Tsai WH, Wang PW, Wu IL, Lin SY, Chen YL, Chen JY, Lin SF (2012) Suppressive regulation of KSHV RTA with O-GlcNAcylation. J Biomed Sci 19:12
        doi: 10.1186/1423-0127-19-12

    139. Koyano S, Mar EC, Stamey FR, Inoue N (2003) Glycoproteins M and N of human herpesvirus 8 form a complex and inhibit cell fusion. J Gen Virol 84:1485-1491
        doi: 10.1099/vir.0.18941-0

    140. Krishnan HH, Sharma-Walia N, Zeng L, Gao SJ, Chandran B (2005) Envelope glycoprotein gB of Kaposi's sarcoma-associated herpesvirus is essential for egress from infected cells. J Virol 79:10952-10967
        doi: 10.1128/JVI.79.17.10952-10967.2005

    141. Krithivas A, Fujimuro M, Weidner M, Young DB, Hayward SD (2002) Protein interactions targeting the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus to cell chromosomes. J Virol 76:11596-11604
        doi: 10.1128/JVI.76.22.11596-11604.2002

    142. Krueger A, Baumann S, Krammer PH, Kirchhoff S (2001) FLICE-inhibitory proteins: regulators of death receptor-mediated apoptosis. Mol Cell Biol 21:8247-8254
        doi: 10.1128/MCB.21.24.8247-8254.2001

    143. Lagunoff M, Bechtel J, Venetsanakos E, Roy AM, Abbey N, Herndier B, McMahon M, Ganem D (2002) De novo infection and serial transmission of Kaposi's Sarcoma-associated herpesvirus in cultured endothelial cells. J Virol 76:2440-2448
        doi: 10.1128/jvi.76.5.2440-2448.2002

    144. Lai IY, Farrell PJ, Kellam P (2011) X-box binding protein 1 induces the expression of the lytic cycle transactivator of Kaposi's sarcoma-associated herpesvirus but not Epstein-Barr virus in co-infected primary effusion lymphoma. J Gen Virol 92:421-431
        doi: 10.1099/vir.0.025494-0

    145. Laman H, Coverley D, Krude T, Laskey R, Jones N (2001) Viral cyclin-cyclin-dependent kinase 6 complexes initiate nuclear DNA replication. Mol Cell Biol 21:624-635
        doi: 10.1128/MCB.21.2.624-635.2001

    146. Lan K, Kuppers DA, Verma SC, Robertson ES (2004) Kaposi's sarcoma-associated herpesvirus-encoded latency-associated nuclear antigen inhibits lytic replication by targeting Rta: a potential mechanism for virus-mediated control of latency. J Virol 78:6585-6594
        doi: 10.1128/JVI.78.12.6585-6594.2004

    147. Lan K, Kuppers DA, Robertson ES (2005a) Kaposi's sarcoma-associated herpesvirus reactivation is regulated by interaction of latency-associated nuclear antigen with recombination signal sequence-binding protein Jkappa, the major downstream effector of the Notch signaling pathway. J Virol 79:3468-3478
        doi: 10.1128/JVI.79.6.3468-3478.2005

    148. Lan K, Kuppers DA, Verma SC, Sharma N, Murakami M, Robertson ES (2005b) Induction of Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen by the lytic transactivator RTA: a novel mechanism for establishment of latency. J Virol 79:7453-7465
        doi: 10.1128/JVI.79.12.7453-7465.2005

    149. Lan K, Murakami M, Choudhuri T, Kuppers DA, Robertson ES (2006) Intracellular-activated Notch1 can reactivate Kaposi's sarcoma-associated herpesvirus from latency. Virology 351:393-403
        doi: 10.1016/j.virol.2006.03.047

    150. Lavreys L, Chohan B, Ashley R, Richardson BA, Corey L, Mandaliya K, Ndinya-Achola JO, Kreiss JK (2003) Human herpesvirus 8: seroprevalence and correlates in prostitutes in Mombasa, Kenya. J Infect Dis 187:359-363
        doi: 10.1086/jid.2003.187.issue-3

    151. Lee HR, Lee S, Chaudhary PM, Gill P, Jung JU (2010) Immune evasion by Kaposi's sarcoma-associated herpesvirus. Future Microbiol 5:1349-1365
        doi: 10.2217/fmb.10.105

    152. Lee HR, Brulois K, Wong L, Jung JU (2012) Modulation of immune system by Kaposi's Sarcoma-associated herpesvirus: lessons from viral evasion strategies. Front Microbiol 3:44

    153. Lee HR, Choi UY, Hwang SW, Kim S, Jung JU (2016a) Viral inhibition of PRR-mediated innate immune response: learning from KSHV evasion strategies. Mol Cells 39:777-782
        doi: 10.14348/molcells.2016.0232

    154. Lee HR, Mitra J, Lee S, Gao SJ, Oh TK, Kim MH, Ha T, Jung JU (2016b) Kaposi's Sarcoma-associated herpesvirus viral interferon regulatory factor 4 (vIRF4) perturbs the G1-S cell cycle progression via deregulation of the cyclin D1 gene. J Virol 90:1139-1143
        doi: 10.1128/JVI.01897-15

    155. Lee MS, Yuan H, Jeon H, Zhu Y, Yoo S, Shi S, Krueger B, Renne R, Lu C, Jung JU, Gao SJ (2016c) Human mesenchymal stem cells of diverse origins support persistent infection with Kaposi's sarcoma-associated herpesvirus and manifest distinct angiogenic, invasive, and transforming phenotypes. MBio 7:e02109-e02115

    156. Lei X, Bai Z, Ye F, Xie J, Kim CG, Huang Y, Gao SJ (2010) Regulation of NF-kappaB inhibitor IkappaBalpha and viral replication by a KSHV microRNA. Nat Cell Biol 12:193-199
        doi: 10.1038/ncb2019

    157. Lennette ET, Blackbourn DJ, Levy JA (1996) Antibodies to human herpesvirus type 8 in the general population and in Kaposi's sarcoma patients. Lancet 348:858-861
        doi: 10.1016/S0140-6736(96)03240-0

    158. Li J, Huang Y, Cockerell CJ, Friedman-Kien AE (1996) Localization of human herpes-like virus type 8 in vascular endothelial cells and perivascular spindle-shaped cells of Kaposi's Sarcoma lesions by in situ hybridization. Am J Pathol 148:1741-1748

    159. Li M, Lee H, Yoon DW, Albrecht JC, Fleckenstein B, Neipel F, Jung JU (1997) Kaposi's sarcoma-associated herpesvirus encodes a functional cyclin. J Virol 71:1984-1991

    160. Li FY, Jeffrey PD, Yu JW, Shi Y (2006) Crystal structure of a viral FLIP: insights into FLIP-mediated inhibition of death receptor signaling. J Biol Chem 281:2960-2968
        doi: 10.1074/jbc.M511074200

    161. Li Q, Zhou F, Ye F, Gao SJ (2008) Genetic disruption of KSHV major latent nuclear antigen LANA enhances viral lytic transcriptional program. Virology 379:234-244
        doi: 10.1016/j.virol.2008.06.043

    162. Li W, Avey D, Fu B, Wu JJ, Ma S, Liu X, Zhu F (2016a) Kaposi's sarcoma-associated herpesvirus inhibitor of cGAS (KicGAS), encoded by ORF52, is an abundant tegument protein and is required for production of infectious progeny viruses. J Virol 90:5329-5342
        doi: 10.1128/JVI.02675-15

    163. Li W, Jia XM, Shen C, Zhang M, Xu J, Shang Y, Zhu K, Hu M, Yan Q, Qin D, Lee M, Zhu J, Lu H, Krueger BJ, Renne R, Gao SJ, Lu C (2016b) A KSHV microRNA enhances viral latency and induces angiogenesis by targeting GRK2 to activate the CXCR164/AKT pathway. Oncotarget 7:32286-32305

    164. Li W, Yan Q, Ding X, Shen C, Hu M, Zhu Y, Qin D, Lu H, Krueger BJ, Renne R, Gao SJ, Lu C (2016c) The SH3BGR/STAT3 pathway regulates cell migration and angiogenesis induced by a gammaherpesvirus MicroRNA. PLoS Pathog 12:e1005605
        doi: 10.1371/journal.ppat.1005605

    165. Li W, Hu M, Wang C, Lu H, Chen F, Xu J, Shang Y, Wang F, Qin J, Yan Q, Krueger BJ, Renne R, Gao SJ, Lu C (2017) A viral microRNA downregulates metastasis suppressor CD82 and induces cell invasion and angiogenesis by activating the c-Met signaling. Oncogene 36:5407-5420
        doi: 10.1038/onc.2017.139

    166. Li Y, Zhong C, Liu D, Yu W, Chen W, Wang Y, Shi S, Yuan Y (2018) Evidence for Kaposi sarcoma originating from Mesenchymal stem cell through KSHV-induced Mesenchymal-to-endothelial transition. Cancer Res 78:230-245

    167. Liang D, Gao Y, Lin X, He Z, Zhao Q, Deng Q, Lan K (2011) A human herpesvirus miRNA attenuates interferon signaling and contributes to maintenance of viral latency by targeting IKK epsilon. Cell Res 21:793-806
        doi: 10.1038/cr.2011.5

    168. Liao W, Tang Y, Lin SF, Kung HJ, Giam CZ (2003) K-bZIP of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) binds KSHV/HHV-8 Rta and represses Rta-Mediated transactivation. J Virol 77:3809-3815
        doi: 10.1128/JVI.77.6.3809-3815.2003

    169. Lim C, Sohn H, Gwack Y, Choe J (2000) Latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8) binds ATF4/CREB2 and inhibits its transcriptional activation activity. J Gen Virol 81:2645-2652
        doi: 10.1099/0022-1317-81-11-2645

    170. Lim C, Sohn H, Lee D, Gwack Y, Choe J (2002) Functional dissection of latency-associated nuclear antigen 1 of Kaposi's sarcoma-associated herpesvirus involved in latent DNA replication and transcription of terminal repeats of the viral genome. J Virol 76:10320-10331
        doi: 10.1128/JVI.76.20.10320-10331.2002

    171. Lin C, Li H, Wang Y, Zhu FX, Kudchodkar S, Yuan Y (2003) Kaposi's Sarcoma-associated herpesvirus lytic origin (ori-Lyt)-dependent DNA replication: identification of the ori-Lyt and association of K8 bZip protein with the origin. J Virol 77:5578-5588
        doi: 10.1128/JVI.77.10.5578-5588.2003

    172. Lin X, Liang D, He Z, Deng Q, Robertson E, Lan K (2011) miR-K12-7-5p encoded by Kaposi's sarcoma-associated herpesvirus stabilizes the latent state by targeting viral ORF50/RTA. PLoS ONE 6:e16224
        doi: 10.1371/journal.pone.0016224

    173. Lin X, Li X, Liang D, Lan K (2012) MicroRNAs and unusual small RNAs discovered in Kaposi's sarcoma-associated herpesvirus virions. J Virol 86:12717-12730
        doi: 10.1128/JVI.01473-12

    174. Lisco A, Barbierato M, Fiore JR, Gasperini P, Favia A, Volpe A, Chironna M, Pastore G, Chieco-Bianchi L, Calabro ML (2006) Pregnancy and human herpesvirus 8 reactivation in human immunodeficiency virus type 1-infected women. J Clin Microbiol 44:3863-3871
        doi: 10.1128/JCM.00791-06

    175. Liu Z, Fang Q, Zhou S, Minhas V, Wood C, He N, Zhang T (2017) Seroprevalence of Kaposi's sarcoma-associated herpesvirus among HIV-infected Uygurs in Xinjiang, China. J Med Virol 89:1629-1635
        doi: 10.1002/jmv.v89.9

    176. Liu D, Wang Y, Yuan Y (2018) Kaposi's sarcoma-associated herpesvirus K8 is an RNA binding protein that regulates viral DNA replication in coordination with a noncoding RNA. J Virol 92:e02177-17

    177. Lock MJ, Thorley N, Teo J, Emery VC (2002) Azidodeoxythymidine and didehydrodeoxythymidine as inhibitors and substrates of the human herpesvirus 8 thymidine kinase. J Antimicrob Chemother 49:359-366
        doi: 10.1093/jac/49.2.359

    178. Lu F, Zhou J, Wiedmer A, Madden K, Yuan Y, Lieberman PM (2003) Chromatin remodeling of the Kaposi's sarcoma-associated herpesvirus ORF50 promoter correlates with reactivation from latency. J Virol 77:11425-11435
        doi: 10.1128/JVI.77.21.11425-11435.2003

    179. Lu F, Day L, Gao SJ, Lieberman PM (2006) Acetylation of the latency-associated nuclear antigen regulates repression of Kaposi's sarcoma-associated herpesvirus lytic transcription. J Virol 80:5273-5282
        doi: 10.1128/JVI.02541-05

    180. Lu CC, Li Z, Chu CY, Feng J, Feng J, Sun R, Rana TM (2010) MicroRNAs encoded by Kaposi's sarcoma-associated herpesvirus regulate viral life cycle. EMBO Rep 11:784-790
        doi: 10.1038/embor.2010.132

    181. Lukac DM, Kirshner JR, Ganem D (1999a) Transcriptional activation by the product of open reading frame 50 of Kaposi's Sarcoma-associated herpesvirus is required for lytic viral reactivation in B cells. J Virol 73:9348-9361

    182. Lukac DM, Kirshner JR, Ganem D (1999b) Transcriptional activation by the product of open reading frame 50 of Kaposi's sarcoma-associated herpesvirus Is required for lytic viral reactivation in B cells. J Virol 73:9348-9361

    183. Lukac DM, Garibyan L, Kirshner JR, Palmeri D, Ganem D (2001) DNA binding by Kaposi's sarcoma-associated herpesvirus lytic switch protein is necessary for transcriptional activation of two viral delayed early promoters. J Virol 75:6786-6799
        doi: 10.1128/JVI.75.15.6786-6799.2001

    184. Majerciak V, Zheng ZM (2009) Kaposi's sarcoma-associated herpesvirus ORF57 in viral RNA processing. Front Biosci 14:1516-1528

    185. Majerciak V, Zheng ZM (2015) KSHV ORF57, a protein of many faces. Viruses 7:604-633
        doi: 10.3390/v7020604

    186. Majerciak V, Zheng ZM (2016) Alternative RNA splicing of KSHV ORF57 produces two different RNA isoforms. Virology 488:81-87
        doi: 10.1016/j.virol.2015.10.031

    187. Majerciak V, Yamanegi K, Nie SH, Zheng ZM (2006a) Structural and functional analyses of Kaposi sarcoma-associated herpesvirus ORF57 nuclear localization signals in living cells. J Biol Chem 281:28365-28378
        doi: 10.1074/jbc.M603095200

    188. Majerciak V, Yamanegi K, Zheng ZM (2006b) Gene structure and expression of Kaposi's sarcoma-associated herpesvirus ORF56, ORF57, ORF58, and ORF59. J Virol 80:11968-11981
        doi: 10.1128/JVI.01394-06

    189. Majerciak V, Pripuzova N, McCoy JP, Gao SJ, Zheng ZM (2007) Targeted disruption of Kaposi's sarcoma-associated herpesvirus ORF57 in the viral genome is detrimental for the expression of ORF59, K8alpha, and K8.1 and the production of infectious virus. J Virol 81:1062-1071

    190. Majerciak V, Yamanegi K, Allemand E, Kruhlak M, Krainer AR, Zheng ZM (2008) Kaposi's sarcoma-associated herpesvirus ORF57 functions as a viral splicing factor and promotes expression of intron-containing viral lytic genes in spliceosome-mediated RNA splicing. J Virol 82:2792-2801
        doi: 10.1128/JVI.01856-07

    191. Majerciak V, Uranishi H, Kruhlak M, Pilkington GR, Massimelli MJ, Bear J, Pavlakis GN, Felber BK, Zheng ZM (2011) Kaposi's sarcoma-associated herpesvirus ORF57 interacts with cellular RNA export cofactors RBM15 and OTT3 to promote expression of viral ORF59. J Virol 85:1528-1540
        doi: 10.1128/JVI.01709-10

    192. Majerciak V, Ni T, Yang W, Meng B, Zhu J, Zheng ZM (2013) A viral genome landscape of RNA polyadenylation from KSHV latent to lytic infection. PLoS Pathog 9:e1003749
        doi: 10.1371/journal.ppat.1003749

    193. Majerciak V, Lu M, Li X, Zheng ZM (2014) Attenuation of the suppressive activity of cellular splicing factor SRSF3 by Kaposi sarcoma-associated herpesvirus ORF57 protein is required for RNA splicing. RNA 20:1747-1758
        doi: 10.1261/rna.045500.114

    194. Majerciak V, Pripuzova N, Chan C, Temkin N, Specht SI, Zheng ZM (2015) Stability of structured Kaposi's sarcoma-associated herpesvirus ORF57 protein is regulated by protein phosphorylation and homodimerization. J Virol 89:3256-3274
        doi: 10.1128/JVI.03721-14

    195. Malik P, Blackbourn DJ, Clements JB (2004) The evolutionarily conserved Kaposi's sarcoma-associated herpesvirus ORF57 protein interacts with REF protein and acts as an RNA export factor. J Biol Chem 279:33001-33011
        doi: 10.1074/jbc.M313008200

    196. Malope BI, MacPhail P, Mbisa G, MacPhail C, Stein L, Ratshikhopha EM, Ndhlovu L, Sitas F, Whitby D (2008) No evidence of sexual transmission of Kaposi's sarcoma herpes virus in a heterosexual South African population. AIDS 22:519-526
        doi: 10.1097/QAD.0b013e3282f46582

    197. Mantina H, Kankasa C, Klaskala W, Brayfield B, Campbell J, Du Q, Bhat G, Kasolo F, Mitchell C, Wood C (2001) Vertical transmission of Kaposi's sarcoma-associated herpesvirus. Int J Cancer 94:749-752
        doi: 10.1002/(ISSN)1097-0215

    198. Martin JN, Ganem D, Osmond DH, Page-Shafer KA, Macrae D, Kedes DH (1998) Sexual transmission and the natural history of human herpesvirus 8 infection. N Engl J Med 338:948-954
        doi: 10.1056/NEJM199804023381403

    199. Martinez FP, Tang Q (2012) Leucine zipper domain is required for Kaposi sarcoma-associated herpesvirus (KSHV) K-bZIP protein to interact with histone deacetylase and is important for KSHV replication. J Biol Chem 287:15622-15634
        doi: 10.1074/jbc.M111.315861

    200. Massimelli MJ, Kang JG, Majerciak V, Le SY, Liewehr DJ, Steinberg SM, Zheng ZM (2011) Stability of a long noncoding viral RNA depends on a 9-nt core element at the RNA 5′ end to interact with viral ORF57 and cellular PABPC1. Int J Biol Sci 7:1145-1160
        doi: 10.7150/ijbs.7.1145

    201. Massimelli MJ, Majerciak V, Kruhlak M, Zheng ZM (2013) Interplay between polyadenylate-binding protein 1 and Kaposi's sarcoma-associated herpesvirus ORF57 in accumulation of polyadenylated nuclear RNA, a viral long noncoding RNA. J Virol 87:243-256
        doi: 10.1128/JVI.01693-12

    202. Massimelli MJ, Majerciak V, Kang JG, Liewehr DJ, Steinberg SM, Zheng ZM (2015) Multiple regions of Kaposi's sarcoma-associated herpesvirus ORF59 RNA are required for its expression mediated by viral ORF57 and cellular RBM15. Viruses 7:496-510
        doi: 10.3390/v7020496

    203. Matta H, Sun Q, Moses G, Chaudhary PM (2003) Molecular genetic analysis of human herpes virus 8-encoded viral FLICE inhibitory protein-induced NF-kappaB activation. J Biol Chem 278:52406-52411
        doi: 10.1074/jbc.M307308200

    204. Matta H, Mazzacurati L, Schamus S, Yang T, Sun Q, Chaudhary PM (2007) Kaposi's sarcoma-associated herpesvirus (KSHV) oncoprotein K13 bypasses TRAFs and directly interacts with the IkappaB kinase complex to selectively activate NF-kappaB without JNK activation. J Biol Chem 282:24858-24865
        doi: 10.1074/jbc.M700118200

    205. Matta H, Gopalakrishnan R, Graham C, Tolani B, Khanna A, Yi H, Suo Y, Chaudhary PM (2012) Kaposi's sarcoma associated herpesvirus encoded viral FLICE inhibitory protein K13 activates NF-kappaB pathway independent of TRAF6, TAK1 and LUBAC. PLoS ONE 7:e36601
        doi: 10.1371/journal.pone.0036601

    206. McAllister SC, Hansen SG, Ruhl RA, Raggo CM, DeFilippis VR, Greenspan D, Früh K, Moses AV (2004) Kaposi sarcoma-associated herpesvirus (KSHV) induces heme oxygenase-1 expression and activity inKSHV-infected endothelial cells. Blood 103:3465-3473
        doi: 10.1182/blood-2003-08-2781

    207. McCormick C, Ganem D (2005) The Kaposin B protein of KSHV activates the p38/MK2 pathway and stabilizes cytokine mRNAs. Science 307:739-741
        doi: 10.1126/science.1105779

    208. Meade-Tollin LC, Way D, Witte MH (1999) Expression of multiple matrix metalloproteinases and urokinase type plasminogen activator in cultured Kaposi sarcoma cells. Acta Histochem 101:305-316
        doi: 10.1016/S0065-1281(99)80031-2

    209. Melbye M, Cook PM, Hjalgrim H, Begtrup K, Simpson GR, Biggar RJ, Ebbesen P, Schulz TF (1998) Risk factors for Kaposi's-sarcoma-associated herpesvirus (KSHV/HHV-8) seropositivity in a cohort of homosexual men, 1981-1996. Int J Cancer 77:543-548
        doi: 10.1002/(ISSN)1097-0215

    210. Miller G, Heston L, Grogan E, Gradoville L, Rigsby M, Sun R, Shedd D, Kushnaryov VM, Grossberg S, Chang Y (1997) Selective switch between latency and lytic replication of Kaposi's sarcoma herpesvirus and Epstein-Barr virus in dually infected body cavity lymphoma cells. J Virol 71:314-324

    211. Miller G, El-Guindy A, Countryman J, Ye J, Gradoville L (2007) Lytic cycle switches of oncogenic human gammaherpesviruses 1. Adv Cancer Res 97:81-109
        doi: 10.1016/S0065-230X(06)97004-3

    212. Minhas V, Wood C (2014) Epidemiology and transmission of Kaposi's sarcoma-associated herpesvirus. Viruses 6:4178-4194
        doi: 10.3390/v6114178

    213. Molden J, Chang Y, You Y, Moore PS, Goldsmith MA (1997) A Kaposi's sarcoma-associated herpesvirus-encoded cytokine homolog (vIL-6) activates signaling through the shared gp130 receptor subunit. J Biol Chem 272:19625-19631
        doi: 10.1074/jbc.272.31.19625

    214. Moldovan GL, Pfander B, Jentsch S (2007) PCNA, the maestro of the replication fork. Cell 129:665-679
        doi: 10.1016/j.cell.2007.05.003

    215. Mollica L, Bessa LM, Hanoulle X, Jensen MR, Blackledge M, Schneider R (2016) binding mechanisms of intrinsically disordered proteins: theory, simulation, and experiment. Front Mol Biosci 3:52

    216. Moody R, Zhu Y, Huang Y, Cui X, Jones T, Bedolla R, Lei X, Bai Z, Gao SJ (2013) KSHV microRNAs mediate cellular transformation and tumorigenesis by redundantly targeting cell growth and survival pathways. PLoS Pathog 9:e1003857
        doi: 10.1371/journal.ppat.1003857

    217. Moore PS, Chang Y (2003) Kaposi's sarcoma-associated herpesvirus immunoevasion and tumorigenesis: two sides of the same coin? Annu Rev Microbiol 57:609-639
        doi: 10.1146/annurev.micro.57.030502.090824

    218. Muralidhar S, Pumfery AM, Hassani M, Reza Sadaie M, Azumi N, Kishishita M, Brady JN, Doniger J, Medveczky P, Rosenthal LJ (1998) Identification of Kaposin (open reading frame K12) as a human Herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) transforming gene. J Virol 72:4980-4988

    219. Myoung J, Ganem D (2011a) Generation of a doxycycline-inducible KSHV producer cell line of endothelial origin: maintenance of tight latency with efficient reactivation upon induction. J Virol Methods 174:12-21
        doi: 10.1016/j.jviromet.2011.03.012

    220. Myoung J, Ganem D (2011b) Infection of primary human tonsillar lymphoid cells by KSHV reveals frequent but abortive infection of T cells. Virology 413:1-11
        doi: 10.1016/j.virol.2010.12.036

    221. Nachmani D, Stern-Ginossar N, Sarid R, Mandelboim O (2009) Diverse herpesvirus microRNAs target the stress-induced immune ligand MICB to escape recognition by natural killer cells. Cell Host Microbe 5:376-385
        doi: 10.1016/j.chom.2009.03.003

    222. Nakamura H, Lu M, Gwack Y, Souvlis J, Zeichner SL, Jung JU (2003) Global changes in Kaposi's sarcoma-associated virus gene expression patterns following expression of a tetracycline-inducible Rta transactivator. J Virol 77:4205-4220
        doi: 10.1128/JVI.77.7.4205-4220.2003

    223. Naranatt PP, Akula SM, Chandran B (2002) Characterization of gamma2-human herpesvirus-8 glycoproteins gH and gL. Arch Virol 147:1349-1370
        doi: 10.1007/s00705-002-0813-7

    224. Neipel F, Albrecht JC, Fleckenstein B (1997) Cell-homologous genes in the Kaposi's sarcoma-associated Rhadinovirus Human Herpesvirus 8: determinants of its pathogenicity? J Virol 71:4187-4192

    225. Nekorchuk M, Han Z, Hsieh TT, Swaminathan S (2007) Kaposi's sarcoma-associated herpesvirus ORF57 protein enhances mRNA accumulation independently of effects on nuclear RNA export. J Virol 81:9990-9998
        doi: 10.1128/JVI.00896-07

    226. O'Byrne KJ, Dalgleish AG, Browning MJ, Steward WP, Harris AL (2000) The relationship between angiogenesis and the immune response in carcinogenesis and the progression of malignant disease. Eur J Cancer 36:151-169
        doi: 10.1016/S0959-8049(99)00241-5

    227. Ohlsson R, Renkawitz R, Labanenkov V (2001) CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease. Trends Genet 17:520-527
        doi: 10.1016/S0168-9525(01)02366-6

    228. Ohsaki E, Ueda K (2012) Kaposi's sarcoma-associated herpesvirus genome replication, partitioning, and maintenance in latency. Front Microbiol 3:7

    229. Ohsaki E, Ueda K, Sakakibara S, Do E, Yada K, Yamanishi K (2004) Poly(ADP-ribose) polymerase 1 binds to Kaposi's sarcoma-associated herpesvirus (KSHV) terminal repeat sequence and modulates KSHV replication in latency. J Virol 78:9936-9946
        doi: 10.1128/JVI.78.18.9936-9946.2004

    230. Okroj M, Tedeschi R, Mancuso R, Brambilla L, Tourlaki A, Dillner J, Blom AM (2011) Prevalence of antibodies against Kaposi's sarcoma associated herpes virus (KSHV) complement inhibitory protein (KCP) in KSHV-related diseases and their correlation with clinical parameters. Vaccine 29:1129-1134
        doi: 10.1016/j.vaccine.2010.11.070

    231. Orenstein JM (2008) Ultrastructure of Kaposi Sarcoma. Ultrastruct Pathol 32:211-220
        doi: 10.1080/01913120802343871

    232. Ottinger M, Christalla T, Nathan K, Brinkmann MM, Viejo-Borbolla A, Schulz TF (2006) Kaposi's sarcoma-associated herpesvirus LANA-1 interacts with the short variant of BRD4 and releases cells from a BRD4- and BRD2/RING3-induced G1 cell cycle arrest. J Virol 80:10772-10786
        doi: 10.1128/JVI.00804-06

    233. Patel V, Dahlroth SL, Rajakannan V, Ho HT, Cornvik T, Nordlund P (2015) Structure of the C-terminal domain of the multifunctional ICP27 protein from herpes simplex virus 1. J Virol 89:8828-8839
        doi: 10.1128/JVI.00441-15

    234. Paul AG, Chandran B, Sharma-Walia N (2013) Cyclooxygenase-2-prostaglandin E2-eicosanoid receptor inflammatory axis: a key player in Kaposi's sarcoma-associated herpes virus associated malignancies. Transl Res 162:77-92
        doi: 10.1016/j.trsl.2013.03.004

    235. Pearce M, Matsumura S, Wilson AC (2005) Transcripts encoding K12, v-FLIP, v-cyclin, and the microRNA cluster of Kaposi's sarcoma-associated herpesvirus originate from a common promoter. J Virol 79:14457-14464
        doi: 10.1128/JVI.79.22.14457-14464.2005

    236. Persson LM, Wilson AC (2010) Wide-scale use of Notch signaling factor CSL/RBP-Jkappa in RTA-mediated activation of Kaposi's sarcoma-associated herpesvirus lytic genes. J Virol 84:1334-1347
        doi: 10.1128/JVI.01301-09

    237. Pertel PE (2002) Human herpesvirus 8 glycoprotein B (gB), gH, and gL can mediate cell fusion. J Virol 76:4390-4400
        doi: 10.1128/JVI.76.9.4390-4400.2002

    238. Pfeffer S, Sewer A, Lagos-Quintana M, Sheridan R, Sander C, Grässer FA, van Dyk LF, Ho CK, Shuman S, Chien M, Russo JJ, Ju J, Randall G, Lindenbach BD, Rice CM, Simon V, Ho DD, Zavolan M, Tuschl T (2005) Identification of microRNAs of the herpesvirus family. Nat Methods 2:269-276
        doi: 10.1038/nmeth746

    239. Picchio GR, Sabbe RE, Gulizia RJ, Mcgrath M, Herndier BG, Moiser DE (1997) The KSHV/HHV8-infected BCBL-1 lymphoma line causes tumors in SCID Mice but fails to transmit virus to a human peripheral blood mononuclear cell graft. J Virol Methods 238:22-29

    240. Pilkington GR, Majerciak V, Bear J, Uranishi H, Zheng ZM, Felber BK (2012) Kaposi's sarcoma-associated herpesvirus ORF57 is not a bona fide export factor. J Virol 86:13089-13094
        doi: 10.1128/JVI.00606-12

    241. Purushothaman P, McDowell ME, McGuinness J, Salas R, Rumjahn SM, Verma SC (2012) Kaposi's sarcoma-associated herpesvirus-encoded LANA recruits topoisomerase IIbeta for latent DNA replication of the terminal repeats. J Virol 86:9983-9994
        doi: 10.1128/JVI.00839-12

    242. Purushothaman P, Thakker S, Verma SC (2015) Transcriptome analysis of Kaposi's sarcoma-associated herpesvirus during de novo primary infection of human B and endothelial cells. J Virol 89:3093-3111
        doi: 10.1128/JVI.02507-14

    243. Purushothaman P, Uppal T, Sarkar R, Verma SC (2016) KSHV-mediated angiogenesis in tumor progression. Viruses 8:E198
        doi: 10.3390/v8070198

    244. Qin J, Li W, Gao SJ, Lu C (2017) KSHV microRNAs: tricks of the devil. Trends Microbiol 25:648-661
        doi: 10.1016/j.tim.2017.02.002

    245. Quinlivan EB, Zhang C, Stewart PW, Komoltri C, Davis MG, Wehbie RS (2002) Elevated virus loads of Kaposi's sarcoma-associated human herpesvirus 8 predict Kaposi's sarcoma disease progression, but elevated levels of human immunodeficiency virus type 1 do not. J Infect Dis 185:1736-1744
        doi: 10.1086/jid.2002.185.issue-12

    246. Radkov SA, Kellam R, Boshoff C (2000) The latent nuclear antigen of Kaposi sarcoma-associated herpesvirus targets the retinoblastoma-E2F pathway and with the oncogene Hras transforms primary rat cells. Nat Med 6:1121-1127
        doi: 10.1038/80459

    247. Radu O, Pantanowitz L (2013) Kaposi Sarcoma. Arch Pathol Lab Med 137:289-294
        doi: 10.5858/arpa.2012-0101-RS

    248. Ramalingam D, Happel C, Ziegelbauer JM (2015) Kaposi's sarcoma-associated herpesvirus microRNAs repress breakpoint cluster region protein expression, enhance Rac1 activity, and increase in vitro angiogenesis. J Virol 89:4249-4261
        doi: 10.1128/JVI.03687-14

    249. Rappocciolo G, Jenkins FJ, Hensler HR, Piazza P, Jais M, Borowski L, Watkins SC, Rinaldo CR (2006) DC-SIGN is a receptor for human herpesvirus 8 on dendritic cells and macrophages. J Immunol 176:1741-1749
        doi: 10.4049/jimmunol.176.3.1741

    250. Renne R, Lagunoff M, Zhong W, Ganem D (1996a) The size and conformation of Kaposi's Sarcoma-associated Herpesvirus (Human Herpesvirus 8) DNA in infected cells and virions. J Virol 70:8151-8154

    251. Renne R, Zhong W, Herndier B, Mcgrath M, Abbey N, Kedes D, Ganem D (1996b) Lytic growth of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in culture. Nat Med 2:342-346
        doi: 10.1038/nm0396-342

    252. Renne R, Dittmer D, Kedes D, Schmidt K, Desrosiers RC, Luciw PA, Ganem D (2004) Experimental transmission of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) to SIV-positive and SIV-negative rhesus macaques. J Med Primatol 33:1-9
        doi: 10.1046/j.1600-0684.2003.00043.x

    253. Revilla-López J, Mendoza-Fabián R, Anampa-Guzmán A, Rosales-Zúñiga J, Chalco-Huamán J (2015) Sarcoma de Kaposi endemico en un paciente VIH negativo. Rev Peru Med Exp Salud Publica 32:808-812
        doi: 10.17843/rpmesp.2015.324.1776

    254. Rivas C, Thlick AE, Parravicini C, Moore PS, Chang Y (2001) Kaposi's sarcoma-associated herpesvirus LANA2 is a B-cell-specific latent viral protein that inhibits p53. J Virol 75:429-438
        doi: 10.1128/JVI.75.1.429-438.2001

    255. Russo JJ, Bohenzky RA, Chien MC, Chen J, Yan M, Maddalena D, Parry JP, Peruzzi D, Edelman IS, Chang Y, Moore P (1996) Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). Proc Natl Acad Sci USA 93:14862-14867
        doi: 10.1073/pnas.93.25.14862

    256. Sadagopan S, Sharma-Walia N, Veettil MV, Bottero V, Levine R, Vart RJ, Chandran B (2009) Kaposi's sarcoma-associated herpesvirus upregulates angiogenin during infection of human dermal microvascular endothelial cells, which induces 45S rRNA synthesis, antiapoptosis, cell proliferation, migration, and angiogenesis. J Virol 83:3342-3364
        doi: 10.1128/JVI.02052-08

    257. Sadler R, Wu L, Forghani B, Renne R, Zhong W, Herndier B, Ganem D (1999) A complex translational program generates multiple novel proteins from the latently expressed kaposin (K12) locus of Kaposi's sarcoma-associated herpesvirus. J Virol 73:5722-5730

    258. Sakakibara S, Tosato G (2009) Regulation of angiogenesis in malignancies associated with Epstein-Barr virus and Kaposi's sarcoma-associated herpes virus. Future Microbiol 4:903-917
        doi: 10.2217/fmb.09.49

    259. Sarek G, Jarviluoma A, Ojala PM (2006) KSHVviral cyclin inactivates p27KIP1 through Ser10 and Thr187 phosphorylation in proliferating primary effusion lymphomas. Blood 107:725-732
        doi: 10.1182/blood-2005-06-2534

    260. Sarek G, Jarviluoma A, Moore HM, Tojkander S, Vartia S, Biberfeld P, Laiho M, Ojala PM (2010) Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency. PLoS Pathog 6:e1000818
        doi: 10.1371/journal.ppat.1000818

    261. Sarid R, Flore O, Bohenzky RA, Chang Y, Moore PS (1999) Transcription mapping of the Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) genome in a body cavity-based lymphoma cell line (BC-1). J Virol 72:1005-1012

    262. Sathish N, Wang X, Yuan Y (2012) Tegument Proteins of Kaposi's sarcoma-associated herpesvirus and related gamma-herpesviruses. Front Microbiol 3:98

    263. Saveliev AK, Zhu FX, Yuan Y (2002) Transcription mapping and expression patterns of genes in the major immediate-early region of Kaposi's sarcoma-associated herpesvirus. Virology 299:301-314
        doi: 10.1006/viro.2002.1561

    264. Schaefke B, Sun W, Li YS, Fang L, Chen W (2018) The evolution of posttranscriptional regulation. Wiley Interdiscip Rev RNA 9:e1485
        doi: 10.1002/wrna.2018.9.issue-5

    265. Shamay M, Liu J, Li R, Liao G, Shen L, Greenway M, Hu S, Zhu J, Xie Z, Ambinder RF, Qian J, Zhu H, Hayward SD (2012) A protein array screen for Kaposi's sarcoma-associated herpesvirus LANA interactors links LANA to TIP60, PP2A activity, and telomere shortening. J Virol 86:5179-5191
        doi: 10.1128/JVI.00169-12

    266. Sharma NR, Majerciak V, Kruhlak MJ, Zheng ZM (2017) KSHV inhibits stress granule formation by viral ORF57 blocking PKR activation. PLoS Pathog 13:e1006677
        doi: 10.1371/journal.ppat.1006677

    267. Sharma-Walia N, Paul AG, Bottero V, Sadagopan S, Veettil MV, Kerur N, Chandran B (2010) Kaposi's sarcoma associated herpes virus (KSHV) induced COX-2: a key factor in latency, inflammation, angiogenesis, cell survival and invasion. PLoS Pathog 6:e1000777
        doi: 10.1371/journal.ppat.1000777

    268. Sharp TV, Wang HW, Koumi A, Hollyman D, Endo Y, Ye H, Du MQ, Boshoff C (2002) K15 protein of Kaposi's sarcoma-associated herpesvirus is latently expressed and binds to HAX-1, a protein with antiapoptotic function. J Virol 76:802-816
        doi: 10.1128/JVI.76.2.802-816.2002

    269. Shin YC, Nakamura H, Liang X, Feng P, Chang H, Kowalik TF, Jung JU (2006) Inhibition of the ATM/p53 signal transduction pathway by Kaposi's sarcoma-associated herpesvirus interferon regulatory factor 1. J Virol 80:2257-2266
        doi: 10.1128/JVI.80.5.2257-2266.2006

    270. Shin HJ, DeCotiis J, Giron M, Palmeri D, Lukac DM (2014) Histone deacetylase classes Ⅰ and Ⅱ regulate Kaposi's sarcoma-associated herpesvirus reactivation. J Virol 88:1281-1292
        doi: 10.1128/JVI.02665-13

    271. Simpson GR, Schulz TF, Whitby D, Cook PM, Boshoff C, Rainbow L, Howard MR, Gao S-J, Bohenzky RA, Simmonds P, Lee C, de Ruiter A, Hatzakis A, Tedder RS, Weller IVD, Weiss RA, Moore PS (1996) Prevalence of Kaposi's sarcoma associated herpesvirus infection measured by antibodies to recombinant capsid protein and latent immunofluorescence antigen. Lancet 348:1133-1138
        doi: 10.1016/S0140-6736(96)07560-5

    272. Singh VV, Dutta D, Ansari MA, Dutta S, Chandran B (2014) Kaposi's sarcoma-associated herpesvirus induces the ATM and H2AX DNA damage response early during de novo infection of primary endothelial cells, which play roles in latency establishment. J Virol 88:2821-2834
        doi: 10.1128/JVI.03126-13

    273. Skalsky RL, Hu J, Renne R (2007) Analysis of viral cis elements conferring Kaposi's sarcoma-associated herpesvirus episome partitioning and maintenance. J Virol 81:9825-9837
        doi: 10.1128/JVI.00842-07

    274. Smith NA, Sabin CA, Gopal R, Bourboulia D, Labbet W, Boshoff C, Barlow D, Band B, Peters BS, de Ruiter A, Brown DWG, Weiss RA, Best JM, Whitby D (1999) Serologic evidence of Human Herpesvirus 8 transmission by homosexual but not heterosexual sex. J Infect Dis 180:600-606
        doi: 10.1086/jid.1999.180.issue-3

    275. Soulier J, Grollet L, Oksenhendler E, Cacoub P, Cazals-Hatem P, Babinet P, d'Agay MF, Clauvel JP, Raphael M, Degos L, Sigaux F (1995) Kaposi's Sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. Blood 86:1276-1280

    276. Speck SH, Ganem D (2010) Viral latency and its regulation: lessons from the gammaherpesviruses. Cell Host Microbe 8:100-115
        doi: 10.1016/j.chom.2010.06.014

    277. Spiller OB, Robinson M, O'Donnell E, Milligan S, Morgan BP, Davison AJ, Blackbourn DJ (2003) Complement regulation by Kaposi's sarcoma-associated herpesvirus ORF4 protein. J Virol 77:592-599
        doi: 10.1128/JVI.77.1.592-599.2003

    278. Staskus KA, Zhong W, Gebhard K, Herndier B, Wang H, Renne R, Beneke J, Pudney J, Anderson DJ, Ganem D, Haase AT (1997) Kaposi's sarcoma-associated herpesvirus gene expression in endothelial (spindle) tumor cells. J Virol 71:715-719

    279. Stedman W, Deng Z, Lu F, Lieberman PM (2004) ORC, MCM, and histone hyperacetylation at the Kaposi's sarcoma-associated herpesvirus latent replication origin. J Virol 78:12566-12575
        doi: 10.1128/JVI.78.22.12566-12575.2004

    280. Sturzl M, Blasig C, Schreier A, Neipel F, Hohenadl C, Cornali E, Ascherl G, Esser S, Brockmeyer NH, Ekman M, Kaaya EE, Tschachler E, Biberfeld P (1997) Expression of HHV-8 latency-associated T0.7 RNA in spindle cells and endothelial cells of AIDS-associated, classical and African Kaposi's Sarcoma. Int J Cancer 72:68-71

    281. Sturzl M, Hohenadl C, Zietz C, Castanos-Velez E, Wunderlich A, Ascherl G, Biberfeld P, Monini P, Browning PJ, Ensoli B (1999) Expression of K13/v-FLIP gene of human herpesvirus 8 and apoptosis in Kaposi's sarcoma spindle cells. J Natl Cancer Inst 91:1725-1733
        doi: 10.1093/jnci/91.20.1725

    282. Sullivan CS (2007) High conservation of Kaposi sarcoma-associated herpesvirus microRNAs implies important function. J Infect Dis 195:618-620
        doi: 10.1086/522471

    283. Sun R, Lin S, Staskus KA, Gradoville L, Grogan E, Haase A, Miller G (1999) Kinetics of Kaposi's Sarcoma-associated herpesvirus gene expression. J Virol 73:2232-2242

    284. Sun Q, Tsurimoto T, Juillard F, Li L, Li SJ, De León Vázquez E, Chen S, Kaye K (2014a) Kaposi's sarcoma-associated herpesvirus LANA recruits the DNA polymerase clamp loader to mediate efficient replication and virus persistence. Proc Natl Acad Sci USA 111:11816-11821
        doi: 10.1073/pnas.1404219111

    285. Sun R, Liang D, Gao Y, Lan K (2014b) Kaposi's sarcoma-associated herpesvirus-encoded LANA interacts with host KAP1 to facilitate establishment of viral latency. J Virol 88:7331-7344
        doi: 10.1128/JVI.00596-14

    286. Sun Z, Jha HC, Robertson ES (2015) Bub1 in complex with LANA recruits PCNA to regulate kaposi's sarcoma-associated herpesvirus latent replication and DNA translesion synthesis. J Virol 89:10206-10218
        doi: 10.1128/JVI.01524-15

    287. Tan B, Gao SJ (2018) RNA epitranscriptomics: regulation of infection of RNA and DNA viruses by N(6) -methyladenosine (m(6) A). Rev Med Virol 28:e1983
        doi: 10.1002/rmv.v28.4

    288. Tan B, Liu H, Zhang S, da Silva SR, Zhang L, Meng J, Cui X, Yuan H, Sorel O, Zhang S-W, Huang Y, Gao SJ (2017) Viral and cellular N6-methyladenosine and N6, 2′-O-dimethyladenosine epitranscriptomes in the KSHV life cycle. Nat Microbiol 3:108-120

    289. Tang S, Zheng ZM (2002) Kaposi's sarcoma-associated herpesvirus K8 exon 3 contains three 5′-splice sites and harbors a K8.1 transcription start site. J Biol Chem 277:14547-14556
        doi: 10.1074/jbc.M111308200

    290. Tang Q, Qin D, Lv Z, Zhu X, Ma X, Yan Q, Zeng Y, Guo Y, Feng N, Lu C (2012) Herpes simplex virus type 2 triggers reactivation of Kaposi's sarcoma-associated herpesvirus from latency and collaborates with HIV-1 Tat. PLoS ONE 7:e31652
        doi: 10.1371/journal.pone.0031652

    291. Tomkowicz B, Singh SP, Cartas M, Srinivasan A (2002) Human herpesvirus-8 encoded Kaposin: subcellular localization using immunofluorescence and biochemical approaches. DNA Cell Biol 21:151-162
        doi: 10.1089/10445490252925413

    292. Toth Z, Maglinte DT, Lee SH, Lee HR, Wong LY, Brulois KF, Lee S, Buckley JD, Laird PW, Marquez VE, Jung JU (2010) Epigenetic analysis of KSHV latent and lytic genomes. PLoS Pathog 6:e1001013
        doi: 10.1371/journal.ppat.1001013

    293. Toth Z, Brulois K, Jung JU (2013a) The chromatin landscape of Kaposi's sarcoma-associated herpesvirus. Viruses 5:1346-1373
        doi: 10.3390/v5051346

    294. Toth Z, Brulois K, Lee HR, Izumiya Y, Tepper C, Kung HJ, Jung JU (2013b) Biphasic euchromatin-to-heterochromatin transition on the KSHV genome following de novo infection. PLoS Pathog 9:e1003813
        doi: 10.1371/journal.ppat.1003813

    295. Toth Z, Papp B, Brulois K, Choi YJ, Gao SJ, Jung JU (2016) LANA-mediated recruitment of host polycomb repressive complexes onto the KSHV genome during de novo infection. PLoS Pathog 12:e1005878
        doi: 10.1371/journal.ppat.1005878

    296. Tsai WH, Wang PW, Lin SY, Wu IL, Ko YC, Chen YL, Li M, Lin SF (2012) Ser-634 and Ser-636 of Kaposi's sarcoma-associated herpesvirus RTA are involved in transactivation and are potential Cdk9 phosphorylation sites. Front Microbiol 3:60

    297. Tsuyama T, Tada S, Watanabe S, Seki M, Enomoto T (2005) Licensing for DNA replication requires a strict sequential assembly of Cdc6 and Cdt1 onto chromatin in Xenopus egg extracts. Nucleic Acids Res 33:765-775
        doi: 10.1093/nar/gki226

    298. Tunnicliffe RB, Schacht M, Levy C, Jowitt TA, Sandri-Goldin RM, Golovanov AP (2015) The structure of the folded domain from the signature multifunctional protein ICP27 from herpes simplex virus-1 reveals an intertwined dimer. Sci Rep 5:11234
        doi: 10.1038/srep11234

    299. Tunnicliffe RB, Collins RF, Ruiz Nivia HD, Sandri-Goldin RM, Golovanov AP (2018) The ICP27 homology domain of the human cytomegalovirus protein UL69 adopts a dimer-of-dimers structure. MBio 9:e01112-e01118

    300. Uldrick TS, Wang V, O'Mahony D, Aleman K, Wyvill KM, Marshall V, Steinberg SM, Pittaluga S, Maric I, Whitby D, Tosato G, Little RF, Yarchoan R (2010) An interleukin-6-related systemic inflammatory syndrome in patients co-infected with Kaposi sarcoma-associated herpesvirus and HIV but without Multicentric Castleman disease. Clin Infect Dis 51:350-358
        doi: 10.1086/652977

    301. Uppal T, Banerjee S, Sun Z, Verma SC, Robertson ES (2014) KSHV LANA-the master regulator of KSHV latency. Viruses 6:4961-4998
        doi: 10.3390/v6124961

    302. Van Bortle K, Corces VG (2013a) The role of chromatin insulators in nuclear architecture and genome function. Curr Opin Genet Dev 23:212-218
        doi: 10.1016/j.gde.2012.11.003

    303. Van Bortle K, Corces VG (2013b) Spinning the web of cell fate. Cell 152:1213-1217
        doi: 10.1016/j.cell.2013.02.052

    304. Van Dross R, Yao S, Asad S, Westlake G, Mays DJ, Barquero L, Duell S, Pietenpol JA, Browning PJ (2005) Constitutively active K-cyclin/cdk6 kinase in Kaposi sarcoma-associated herpesvirus-infected cells. J Natl Cancer Inst 97:656-666
        doi: 10.1093/jnci/dji113

    305. Veettil MV, Bandyopadhyay C, Dutta D, Chandran B (2014) Interaction of KSHV with host cell surface receptors and cell entry. Viruses 6:4024-4046
        doi: 10.3390/v6104024

    306. Verma SC, Borah S, Robertson ES (2004) Latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus up-regulates transcription of human telomerase reverse transcriptase promoter through interaction with transcription factor Sp1. J Virol 78:10348-10359
        doi: 10.1128/JVI.78.19.10348-10359.2004

    307. Verma SC, Choudhuri T, Robertson ES (2007a) The minimal replicator element of the Kaposi's sarcoma-associated herpesvirus terminal repeat supports replication in a semiconservative and cell-cycle-dependent manner. J Virol 81:3402-3413
        doi: 10.1128/JVI.01607-06

    308. Verma SC, Lan K, Choudhuri T, Cotter MA, Robertson ES (2007b) An autonomous replicating element within the KSHV genome. Cell Host Microbe 2:106-118
        doi: 10.1016/j.chom.2007.07.002

    309. Verma SC, Lu J, Cai Q, Kosiyatrakul S, McDowell ME, Schildkraut CL, Robertson ES (2011) Single molecule analysis of replicated DNA reveals the usage of multiple KSHV genome regions for latent replication. PLoS Pathog 7:e1002365
        doi: 10.1371/journal.ppat.1002365

    310. Wang FZ, Akula SM, Pramod NP, Zeng L, Chandran B (2001) Human herpesvirus 8 envelope glycoprotein K8.1A interaction with the target cells involves heparan sulfate. J Virol 75:7517-7527
        doi: 10.1128/JVI.75.16.7517-7527.2001

    311. Wang SE, Wu FY, Yu Y, Hayward GS (2003) CCAAT/enhancer-binding protein is induced during the early stages of Kaposi's sarcoma-associated herpesvirus (KSHV) lytic cycle reactivation and together with the KSHV replication and transcription activator (RTA) cooperatively stimulates the viral RTA, MTA, and PAN promoters. J Virol 77:9590-9612
        doi: 10.1128/JVI.77.17.9590-9612.2003

    312. Wang X, He B, Zhang Z, Liu T, Wang H, Li X, Zhang Q, Lan K, Lu X, Wen H (2010) Human herpesvirus-8 in northwestern China: epidemiology and characterization among blood donors. Virol J 7:62
        doi: 10.1186/1743-422X-7-62

    313. Wang Y, Sathish N, Hollow C, Yuan Y (2011) Functional characterization of Kaposi's sarcoma-associated herpesvirus open reading frame K8 by bacterial artificial chromosome-based mutagenesis. J Virol 85:1943-1957
        doi: 10.1128/JVI.02060-10

    314. Wang L, Kang G, Kumar P, Lu W, Li Y, Zhou Y, Li Q, Wood C (2014) Humanized-BLT mouse model of Kaposi's sarcoma-associated herpesvirus infection. Proc Natl Acad Sci USA 111:3146-3151
        doi: 10.1073/pnas.1318175111

    315. Wang F, Guo Y, Li W, Lu C, Yan Q (2018) Generation of a KSHV K13 deletion mutant for vFLIP function study. J Med Virol 90:753-760
        doi: 10.1002/jmv.v90.4

    316. Wen KW, Damania B (2010) Kaposi sarcoma-associated herpesvirus (KSHV): molecular biology and oncogenesis. Cancer Lett 289:140-150
        doi: 10.1016/j.canlet.2009.07.004

    317. Wen HJ, Minhas V, Wood C (2009) Identification and characterization of a new Kaposi's sarcoma-associated herpesvirus replication and transcription activator (RTA)-responsive element involved in RTA-mediated transactivation. J Gen Virol 90:944-953
        doi: 10.1099/vir.2008.006817-0

    318. Whitby D, Howard MR, Tenant-Flowers M, Brink NS, Copas A, Boshoff C, Hatzioannou T, Suggett FEA, Aldam DM, Denton AS, Miller RF, Weller IVD, Weiss RA, Tedder RS, Schulz TF (1995) Detection of Kaposi sarcoma associated herpesvirus in peripheral blood of HIV-infected individuals and progression to Kaposi's sarcoma. Lancet 346:799-802
        doi: 10.1016/S0140-6736(95)91619-9

    319. Woodard C, Shamay M, Liao G, Zhu J, Ng AN, Li R, Newman R, Rho HS, Hu J, Wan J, Qian J, Zhu H (2012) Phosphorylation of the chromatin binding domain of KSHV LANA. PLoS Pathog 8:e1002972
        doi: 10.1371/journal.ppat.1002972

    320. Wu J, Xu Y, Mo D, Huang P, Sun R, Huang L, Pan S, Xu J (2014) Kaposi's sarcoma-associated herpesvirus (KSHV) vIL-6 promotes cell proliferation and migration by upregulating DNMT1 via STAT3 activation. PLoS ONE 9:e93478
        doi: 10.1371/journal.pone.0093478

    321. Wu JJ, Li W, Shao Y, Avey D, Fu B, Gillen J, Hand T, Ma S, Liu X, Miley W, Konrad A, Neipel F, Sturzl M, Whitby D, Li H, Zhu F (2015) Inhibition of cGAS DNA sensing by a herpesvirus virion protein. Cell Host Microbe 18:333-344
        doi: 10.1016/j.chom.2015.07.015

    322. Xiao B, Verma SC, Cai Q, Kaul R, Lu J, Saha A, Robertson ES (2010) Bub1 and CENP-F can contribute to Kaposi's sarcoma-associated herpesvirus genome persistence by targeting LANA to kinetochores. J Virol 84:9718-9732
        doi: 10.1128/JVI.00713-10

    323. Xie J, Ajibade AO, Ye F, Kuhne K, Gao SJ (2005) Reactivation of Kaposi's sarcoma-associated herpesvirus from latency requires MEK/ERK, JNK and p38 multiple mitogen-activated protein kinase pathways. Virology 371:139-154

    324. Yamanegi K, Tang S, Zheng ZM (2005) Kaposi's sarcoma-associated herpesvirus K8beta is derived from a spliced intermediate of K8 pre-mRNA and antagonizes K8alpha (K-bZIP) to induce p21 and p53 and blocks K8alpha-CDK2 interaction. J Virol 79:14207-14221
        doi: 10.1128/JVI.79.22.14207-14221.2005

    325. Ye F (2017) RNA N6-adenosine methylation (m6A) steers epitranscriptomic control of herpesvirus replication. Inflamm Cell Signal 4:e1604

    326. Ye F, Zhou F, Xie J, Kang T, Greene W, Kuhne K, Lei X, Li Q, Gao SJ (2008) Kaposi's sarcoma-associated herpesvirus latent gene vFLIP inhibits viral lytic replication through NF-kappaB-mediated suppression of the AP-1 pathway: a novel mechanism of virus control of latency. J Virol 82:4235-4249
        doi: 10.1128/JVI.02370-07

    327. Ye F, Lei X, Gao SJ (2011a) Mechanisms of Kaposi's Sarcoma-associated herpesvirus latency and reactivation. Adv Virol 2011:193860

    328. Ye F, Zhou F, Bedolla RG, Jones T, Lei X, Kang T, Guadalupe M, Gao SJ (2011b) Reactive oxygen species hydrogen peroxide mediates Kaposi's sarcoma-associated herpesvirus reactivation from latency. PLoS Pathog 7:e1002054
        doi: 10.1371/journal.ppat.1002054

    329. Ye F, Zhou F, Nithianantham S, Chandran B, Yu X, Weinberg A, Gao SJ (2013) Kaposi's sarcoma-associated herpesvirus induces rapid release of angiopoietin-2 from endothelial cells. J Virol 87:6326-6335
        doi: 10.1128/JVI.03303-12

    330. Ye F, Chen ER, Nilsen TW (2017) Kaposi's sarcoma-associated herpesvirus utilizes and manipulates RNA N6-Adenosine methylation to promote lytic replication. J Virol 91:e00466-00417

    331. Yu F, Harada JN, Brown HJ, Deng H, Song MJ, Wu TT, Kato-Stankiewicz J, Nelson CG, Vieira J, Tamanoi F, Chanda SK, Sun R (2007) Systematic identification of cellular signals reactivating Kaposi sarcoma-associated herpesvirus. PLoS Pathog 3:e44
        doi: 10.1371/journal.ppat.0030044

    332. Yuan F, Gao ZQ, Majerciak V, Bai L, Hu ML, Lin XX, Zheng ZM, Dong YH, Lan K (2018) The crystal structure of KSHV ORF57 reveals dimeric active sites important for protein stability and function. PLoS Pathog 14:e1007232
        doi: 10.1371/journal.ppat.1007232

    333. Zhang T, Liu Z, Wang J, Minhas V, Wood C, Clifford GM, He N, Franceschi S (2017) Seroprevalence of antibodies against Kaposi's sarcoma-associated herpesvirus among HIV-negative people in China. Infect Agent Cancer 12:32
        doi: 10.1186/s13027-017-0142-9

    334. Zhao Q, Liang D, Sun R, Jia B, Xia T, Xiao H, Lan K (2015) Kaposi's sarcoma-associated herpesvirus-encoded replication and transcription activator impairs innate immunity via ubiquitin-mediated degradation of myeloid differentiation factor 88. J Virol 89:415-427
        doi: 10.1128/JVI.02591-14

    335. Zheng ZM (2003) Split genes and their expression in Kaposi's sarcoma-associated herpesvirus. Rev Med Virol 13:173-184
        doi: 10.1002/(ISSN)1099-1654

    336. Zheng J, Yang Y, Cui M, Shu ZJ, Han LL, Liu ZQ, Wood C, Zhang T, Zeng Y (2017) Prevalence of Kaposi's sarcoma-associated herpesvirus in Uygur and Han populations from the Urumqi and Kashgar regions of Xinjiang, China. Virol Sin 32:396-403
        doi: 10.1007/s12250-017-4049-9

    337. Zhou FC, Zhang YJ, Deng JH, Wang XP, Pan HY, Hettler E, Gao SJ (2002) Efficient infection by a recombinant Kaposi's sarcoma-associated herpesvirus cloned in a bacterial artificial chromosome: application for genetic analysis. J Virol 76:6185-6196
        doi: 10.1128/JVI.76.12.6185-6196.2002

    338. Zhu FX, Cusano T, Yuan Y (1999) Identification of the immediate-early transcripts of Kaposi's sarcoma-associated herpesvirus. J Virol 73:5556-5567

    339. Zhu FX, Chong JM, Wu L, Yuan Y (2005) Virion proteins of Kaposi's sarcoma-associated herpesvirus. J Virol 79:800-811
        doi: 10.1128/JVI.79.2.800-811.2005

    340. Ziegelbauer JM, Sullivan CS, Ganem D (2009) Tandem array-based expression screens identify host mRNA targets of virus-encoded microRNAs. Nat Genet 41:130-134
        doi: 10.1038/ng.266

    341. Zoetweij JP, Moses A, Rinderknecht AS, Davis DA, Overwijk WW, Yarchoan R, Orenstein JM, Blauvelt A (2000) Targeted inhibition of calcineurin signaling blocks calcium-dependent reactivation of Kaposi sarcoma-associated herpesvirus. Blood 97:2374-2379

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    Towards Better Understanding of KSHV Life Cycle: from Transcription and Posttranscriptional Regulations to Pathogenesis

      Corresponding author: Zhi-Ming Zheng, zhengt@exchange.nih.gov
      Corresponding author: Ke Lan, klan@whu.edu.cn
    • 1. State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China
    • 2. National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA

    Abstract: Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8 (HHV-8), is etiologically linked to the development of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. These malignancies often occur in immunosuppressed individuals, making KSHV infection-associated diseases an increasing global health concern with persistence of the AIDS epidemic. KSHV exhibits biphasic life cycles between latent and lytic infection and extensive transcriptional and posttranscriptional regulation of gene expression. As a member of the herpesvirus family, KSHV has evolved many strategies to evade the host immune response, which help the virus establish a successful lifelong infection. In this review, we summarize the current research status on the biology of latent and lytic viral infection, the regulation of viral life cycles and the related pathogenesis.