Citation: Joshua L. Justice, Brandy Verhalen, Mengxi Jiang. Polyomavirus interaction with the DNA damage response .VIROLOGICA SINICA, 2015, 30(2) : 122-129.  http://dx.doi.org/10.1007/s12250-015-3583-6

Polyomavirus interaction with the DNA damage response

  • Corresponding author: Mengxi Jiang, mjiang@uab.edu, ORCID: 0000-0002-2222-3606
  • Received Date: 16 March 2015
    Accepted Date: 15 April 2015
    Published Date: 20 April 2015
    Available online: 01 April 2015
  • Viruses are obligate intracellular parasites that subvert cellular metabolism and pathways to mediate their own replication—normally at the expense of the host cell. Polyomaviruses are a group of small DNA viruses, which have long been studied as a model for eukaryotic DNA replication. Polyomaviruses manipulate host replication proteins, as well as proteins involved in DNA maintenance and repair, to serve as essential cofactors for productive infection. Moreover, evidence suggests that polyomavirus infection poses a unique genotoxic threat to the host cell. In response to any source of DNA damage, cells must initiate an effective DNA damage response (DDR) to maintain genomic integrity, wherein two protein kinases, ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR), are major regulators of DNA damage recognition and repair. Recent investigation suggests that these essential DDR proteins are required for productive polyomavirus infection. This review will focus on polyomaviruses and their interaction with ATMand ATR-mediated DNA damage responses and the effect of this interaction on host genomic stability.

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    1. Abend JR, Low JA, Imperiale MJ. 2010. Global effects of BKV infection on gene expression in human primary kidney epithelial cells. Virology, 397: 73-79.
        doi: 10.1016/j.virol.2009.10.047

    2. An P, Saenz Robles MT, Pipas JM. 2012. Large T antigens of polyomaviruses: Amazing molecular machines. Annu Rev Microbiol, 66: 213-236.
        doi: 10.1146/annurev-micro-092611-150154

    3. Andrabi S, Hwang JH, Choe JK, Roberts TM, Schaffhausen BS. 2011. Comparisons between murine polyomavirus and Simian virus 40 show significant differences in small t antigen function. J Virol, 85: 10649-10658.
        doi: 10.1128/JVI.05034-11

    4. Banerjee P, DeJesus R, Gjoerup O, Schaffhausen BS. 2013. Viral interference with DNA repair by targeting of the single-stranded DNA binding protein rpa. PLoS Pathog, 9: e1003725.
        doi: 10.1371/journal.ppat.1003725

    5. Boichuk S, Hu L, Hein J, Gjoerup OV. 2010. Multiple DNA damage signaling and repair pathways deregulated by Simian virus 40 large T antigen. J Virol, 84: 8007-8020.
        doi: 10.1128/JVI.00334-10

    6. Bracken AP, Ciro M, Cocito A, Helin K. 2004. E2F target genes: Unraveling the biology. Trends Biochem Sci, 29: 409-417.
        doi: 10.1016/j.tibs.2004.06.006

    7. Cegielska A, Moarefi I, Fanning E, Virshup DM. 1994. T-antigen kinase inhibits simian virus 40 DNA replication by phospho-rylation of intact T antigen on serines 120 and 123. J Virol, 68: 269-275.

    8. Chaurushiya MS, Weitzman MD. 2009. Viral manipulation of DNA repair and cell cycle checkpoints. DNA Repair (Amst), 8: 1166-1176.
        doi: 10.1016/j.dnarep.2009.04.016

    9. Ciccia A, Elledge SJ. 2010. The DNA damage response: Making it safe to play with knives. Mol Cell, 40: 179-204.
        doi: 10.1016/j.molcel.2010.09.019

    10. Dahl J, You J, Benjamin TL. 2005. Induction and utilization of an ATM signaling pathway by polyomavirus. J Virol, 79: 13007-13017.
        doi: 10.1128/JVI.79.20.13007-13017.2005

    11. DeCaprio JA, Garcea RL. 2013. A cornucopia of human polyoma-viruses. Nat Rev Microbiol, 11: 264-276.
        doi: 10.1038/nrmicro2992

    12. Demetriou SK, Ona-Vu K, Sullivan EM, Dong TK, Hsu SW, Oh DH. 2012. Defective DNA repair and cell cycle arrest in cells expressing merkel cell polyomavirus T antigen. Int J Cancer, 131: 1818-1827.
        doi: 10.1002/ijc.27440

    13. Dey D, Dahl J, Cho S, Benjamin TL. 2002. Induction and bypass of p53 during productive infection by polyomavirus. Journal of Virology, 76: 9526-9532.
        doi: 10.1128/JVI.76.18.9526-9532.2002

    14. Dyson N, Bernards R, Friend SH, Gooding LR, Hassell JA, Major EO, Pipas JM, Vandyke T, Harlow E. 1990. Large T antigens of many polyomaviruses are able to form complexes with the retinoblastoma protein. J Virol, 64: 1353-1356.

    15. Erickson KD, Bouchet-Marquis C, Heiser K, Szomolanyi-Tsuda E, Mishra R, Lamothe B, Hoenger A, Garcea RL. 2012. Virion assembly factories in the nucleus of polyomavirus-infected cells. PLoS Pathog, 8: e1002630.
        doi: 10.1371/journal.ppat.1002630

    16. Feng H, Shuda M, Chang Y, Moore PS. 2008. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science, 319: 1096-1100.
        doi: 10.1126/science.1152586

    17. Garcea RL, Imperiale MJ. 2003. Simian virus 40 infection of humans. J Virol, 77: 5039-5045.
        doi: 10.1128/JVI.77.9.5039-5045.2003

    18. Gjoerup O, Chang Y. 2010. Update on human polyomaviruses and cancer. Adv Cancer Res, 106: 1-51.
        doi: 10.1016/S0065-230X(10)06001-X

    19. Hein J, Boichuk S, Wu J, Cheng Y, Freire R, Jat PS, Roberts TM, Gjoerup OV. 2009. Simian virus 40 large T antigen disrupts genome integrity and activates a DNA damage response via Bub1 binding. J Virol, 83: 117-127.
        doi: 10.1128/JVI.01515-08

    20. Hoeijmakers JH. 2009. DNA damage, aging, and cancer. N Engl J Med, 361: 1475-1485.
        doi: 10.1056/NEJMra0804615

    21. Hu L, Filippakis H, Huang H, Yen TJ, Gjoerup OV. 2013. Replica-tion stress and mitotic dysfunction in cells expressing simian virus 40 large T antigen. J Virol, 87: 13179-13192.
        doi: 10.1128/JVI.02224-13

    22. Jiang M, Zhao L, Gamez M, Imperiale MJ. 2012. Roles of ATM and ATR-mediated DNA damage responses during lytic BK polyomavirus infection. PLoS Pathog, 8: e1002898.
        doi: 10.1371/journal.ppat.1002898

    23. Kassem A, Schopflin A, Diaz C, Weyers W, Stickeler E, Werner M, Zur Hausen A. 2008. Frequent detection of merkel cell polyomavirus in human merkel cell carcinomas and identification of a unique deletion in the VP1 gene. Cancer Res, 68: 5009-5013.
        doi: 10.1158/0008-5472.CAN-08-0949

    24. Li J, Diaz J, Wang X, Tsang SH, You J. 2014. Phosphorylation of merkel cell polyomavirus large T antigen at serine 816 by atm kinase induces apoptosis in host cells. J Biol Chem, 290: 1874-1884.

    25. Li J, Wang X, Diaz J, Tsang SH, Buck CB, You J. 2013. Merkel cell polyomavirus large T antigen disrupts host genomic integrity and inhibits cellular proliferation. J Virol, 87: 9173-9188.
        doi: 10.1128/JVI.01216-13

    26. Lilley CE, Chaurushiya MS, Boutell C, Everett RD, Weitzman MD. 2011. The intrinsic antiviral defense to incoming HSV-1 genomes includes specific DNA repair proteins and is counteracted by the viral protein ICP0. PLoS Pathog, 7: e1002084.
        doi: 10.1371/journal.ppat.1002084

    27. Liu Q, Guntuku S, Cui XS, Matsuoka S, Cortez D, Tamai K, Luo G, Carattini-Rivera S, DeMayo F, Bradley A, Donehower LA, Elledge SJ. 2000. Chk1 is an essential kinase that is regulated by atr and required for the G(2)/M DNA damage checkpoint. Genes Dev, 14: 1448-1459.

    28. Luftig MA. 2014. Viruses and the DNA damage response: Activation and antagonism. Annu Rev Virol, 1: 605-625.
        doi: 10.1146/annurev-virology-031413-085548

    29. Luo Y, Qiu J. 2013. Parvovirus infection-induced DNA damage response. Future Virol, 8: 245-257.
        doi: 10.2217/fvl.13.5

    30. Moens U, Van Ghelue M, Ehlers B. 2014. Are human polyomavi-ruses co-factors for cancers induced by other oncoviruses? Rev Med Virol, 24: 343-360.
        doi: 10.1002/rmv.v24.5

    31. Mullane KP, Ratnofsky M, Cullere X, Schaffhausen B. 1998. Signaling from polyomavirus middle T and small T defines different roles for protein phosphatase 2A. Mol Cell Biol, 18: 7556-7564.
        doi: 10.1128/MCB.18.12.7556

    32. Novoa RR, Calderita G, Arranz R, Fontana J, Granzow H, Risco C. 2005. Virus factories: Associations of cell organelles for viral replication and morphogenesis. Biol Cell, 97: 147-172.
        doi: 10.1042/BC20040058

    33. Okubo E, Lehman JM, Friedrich TD. 2003. Negative regulation of mitotic promoting factor by the checkpoint kinase Chk1 in simian virus 40 lytic infection. J Virol, 77: 1257-1267.
        doi: 10.1128/JVI.77.2.1257-1267.2003

    34. Orba Y, Suzuki T, Makino Y, Kubota K, Tanaka S, Kimura T, Sawa H. 2010. Large T antigen promotes JC virus replication in G2-arrested cells by inducing ATM-and ATR-mediated G2 checkpoint signaling. J Biol Chem, 285: 1544-1554.
        doi: 10.1074/jbc.M109.064311

    35. Pietruska JR, Kane AB. 2007. SV40 oncoproteins enhance asbestos-induced DNA double-strand breaks and abrogate senescence in murine mesothelial cells. Cancer Res, 67: 3637-3645.
        doi: 10.1158/0008-5472.CAN-05-3727

    36. Pinto M, Dobson S. 2014. Bk and jc virus: A review. J Infect, 68 Suppl 1: S2-8.

    37. Pipas JM, Levine AJ. 2001. Role of t antigen interactions with p53 in tumorigenesis. Semin Cancer Biol, 11: 23-30.
        doi: 10.1006/scbi.2000.0343

    38. Pores Fernando AT, Andrabi S, Cizmecioglu O, Zhu C, Livingston DM, Higgins JM, Schaffhausen BS, Roberts TM. 2014. Polyoma small T antigen triggers cell death via mitotic catastrophe. Oncogene. doi: 10.1038/onc.2014.192.

    39. Raghava S, Giorda KM, Romano FB, Heuck AP, Hebert DN. 2011. The SV40 late protein VP4 is a viroporin that forms pores to disrupt membranes for viral release. PLoS Pathog, 7: e1002116.
        doi: 10.1371/journal.ppat.1002116

    40. Rohaly G, Korf K, Dehde S, Dornreiter I. 2010. Simian virus 40 activates ATR-Delta p53 signaling to override cell cycle and DNA replication control. J Virol, 84: 10727-10747.
        doi: 10.1128/JVI.00122-10

    41. Shi Y, Dodson GE, Shaikh S, Rundell K, Tibbetts RS. 2005. Ataxia-telangiectasia-mutated (ATM) is a T-antigen kinase that controls SV40 viral replication in vivo. J Biol Chem, 280: 40195-40200.
        doi: 10.1074/jbc.C500400200

    42. Sowd GA, Li NY, Fanning E. 2013. Atm and atr activities maintain replication fork integrity during SV40 chromatin replication. PLoS Pathog, 9: e1003283.
        doi: 10.1371/journal.ppat.1003283

    43. Sowd GA, Mody D, Eggold J, Cortez D, Friedman KL, Fanning E. 2014. SV40 utilizes ATM kinase activity to prevent non-homologous end joining of broken viral DNA replication products. PLoS Pathog, 10: e1004536.
        doi: 10.1371/journal.ppat.1004536

    44. Stracker TH, Carson CT, Weitzman MD. 2002. Adenovirus oncoproteins inactivate the Mre11-Rad50-Nbs1 DNA repair complex. Nature, 418: 348-352.
        doi: 10.1038/nature00863

    45. Sweet BH, Hilleman MR. 1960. The vacuolating virus, S.V. 40. Proc Soc Exp Biol Med, 105: 420-427.
        doi: 10.3181/00379727-105-26128

    46. Trojanek J, Croul S, Ho T, Wang JY, Darbinyan A, Nowicki M, Del Valle L, Skorski T, Khalili K, Reiss K. 2006. T-antigen of the human polyomavirus jc attenuates faithful DNA repair by forcing nuclear interaction between IRS-1 and Rad51. J Cell Physiol, 206: 35-46.
        doi: 10.1002/jcp.20425

    47. Tsang SH, Wang X, Li J, Buck CB, You J. 2014. Host DNA damage response factors localize to merkel cell polyomavirus DNA replication sites to support efficient viral DNA replication. J Virol, 88: 3285-3297.
        doi: 10.1128/JVI.03656-13

    48. Verhalen B, Justice JL, Imperiale MJ, Jiang M. 2015. Viral DNA replication-dependent DNA damage response activation during bk polyomavirus infection. J Virol, 89: 5032-5039.
        doi: 10.1128/JVI.03650-14

    49. Wileman T. 2007. Aggresomes and pericentriolar sites of virus assembly: Cellular defense or viral design? Annu Rev Microbiol, 61: 149-167.
        doi: 10.1146/annurev.micro.57.030502.090836

    50. Wu X, Avni D, Chiba T, Yan F, Zhao Q, Lin Y, Heng H, Livingston D. 2004. SV40 T antigen interacts with nbs1 to disrupt DNA replication control. Genes Dev, 18: 1305-1316.
        doi: 10.1101/gad.1182804

    51. Yu G, Greninger AL, Isa P, Phan TG, Martinez MA, de la Luz Sanchez M, Contreras JF, Santos-Preciado JI, Parsonnet J, Miller S, DeRisi JL, Delwart E, Arias CF, Chiu CY. 2012. Discovery of a novel polyomavirus in acute diarrheal samples from children. PLoS One, 7: e49449.
        doi: 10.1371/journal.pone.0049449

    52. Zhao X, Madden-Fuentes RJ, Lou BX, Pipas JM, Gerhardt J, Rigell CJ, Fanning E. 2008. Ataxia telangiectasia-mutated damage-signaling kinase-and proteasome-dependent destruction of Mre11-Rad50-Nbs1 subunits in Simian virus 40-infected primate cells. J Virol, 82: 5316-5328.
        doi: 10.1128/JVI.02677-07

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    Polyomavirus interaction with the DNA damage response

      Corresponding author: Mengxi Jiang, mjiang@uab.edu
    • Department of Microbiology, University of Alabama at Birmingham, Birmingham 35294, USA

    Abstract: Viruses are obligate intracellular parasites that subvert cellular metabolism and pathways to mediate their own replication—normally at the expense of the host cell. Polyomaviruses are a group of small DNA viruses, which have long been studied as a model for eukaryotic DNA replication. Polyomaviruses manipulate host replication proteins, as well as proteins involved in DNA maintenance and repair, to serve as essential cofactors for productive infection. Moreover, evidence suggests that polyomavirus infection poses a unique genotoxic threat to the host cell. In response to any source of DNA damage, cells must initiate an effective DNA damage response (DDR) to maintain genomic integrity, wherein two protein kinases, ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR), are major regulators of DNA damage recognition and repair. Recent investigation suggests that these essential DDR proteins are required for productive polyomavirus infection. This review will focus on polyomaviruses and their interaction with ATMand ATR-mediated DNA damage responses and the effect of this interaction on host genomic stability.