Citation: Mariia Novikova, Yulan Zhang, Eric O. Freed, Ke Peng. Multiple Roles of HIV-1 Capsid during the Virus Replication Cycle .VIROLOGICA SINICA, 2019, 34(2) : 119-134.  http://dx.doi.org/10.1007/s12250-019-00095-3

Multiple Roles of HIV-1 Capsid during the Virus Replication Cycle

  • Corresponding author: Eric O. Freed, efreed@nih.gov
    Ke Peng, pengke@wh.iov.cn
  • Received Date: 17 November 2018
    Accepted Date: 16 January 2019
    Published Date: 26 April 2019
    Available online: 01 April 2019
  • Human immunodeficiency virus-1 capsid (HIV-1 CA) is involved in different stages of the viral replication cycle. During virion assembly, CA drives the formation of the hexameric lattice in immature viral particles, while in mature virions CA monomers assemble in cone-shaped cores surrounding the viral RNA genome and associated proteins. In addition to its functions in late stages of the viral replication cycle, CA plays key roles in a number of processes during early phases of HIV-1 infection including trafficking, uncoating, recognition by host cellular proteins and nuclear import of the viral preintegration complex. As a result of efficient cooperation of CA with other viral and cellular proteins, integration of the viral genetic material into the host genome, which is an essential step for productive viral infection, successfully occurs. In this review, we will summarize available data on CA functions in HIV-1 replication, describing in detail its roles in late and early phases of the viral replication cycle.

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    1. Achuthan V, Perreira JM, Sowd GA, Puray-Chavez M, McDougall WM, Paulucci-Holthauzen A, Wu X, Fadel HJ, Poeschla EM, Multani AS, Hughes SH, Sarafianos SG, Brass AL, Engelman AN (2018) Capsid-CPSF6 interaction licenses nuclear HIV-1 trafficking to sites of viral DNA integration. Cell Host Microbe 24(392-404):e398

    2. Adamson CS, Ablan SD, Boeras I, Goila-Gaur R, Soheilian F, Nagashima K, Li F, Salzwedel K, Sakalian M, Wild CT, Freed EO (2006) In vitro resistance to the human immunodeficiency virus type 1 maturation inhibitor PA-457 (Bevirimat). J Virol 80:10957-10971
        doi: 10.1128/JVI.01369-06

    3. Ambrose Z, Aiken C (2014) HIV-1 uncoating: connection to nuclear entry and regulation by host proteins. Virology 454-455:371-379
        doi: 10.1016/j.virol.2014.02.004

    4. Bhattacharya S, Zhang H, Debnath AK, Cowburn D (2008) Solution structure of a hydrocarbon stapled peptide inhibitor in complex with monomeric C-terminal domain of HIV-1 capsid. J Biol Chem 283:16274-16278
        doi: 10.1074/jbc.C800048200

    5. Bhattacharya A, Alam SL, Fricke T, Zadrozny K, Sedzicki J, Taylor AB, Demeler B, Pornillos O, Ganser-Pornillos BK, Diaz-Griffero F, Ivanov DN, Yeager M (2014) Structural basis of HIV-1 capsid recognition by PF74 and CPSF6. Proc Natl Acad Sci USA 111:18625-18630
        doi: 10.1073/pnas.1419945112

    6. Black LR, Aiken C (2010) TRIM5alpha disrupts the structure of assembled HIV-1 capsid complexes in vitro. J Virol 84:6564-6569
        doi: 10.1128/JVI.00210-10

    7. Blair WS, Cao J, Fok-Seang J, Griffin P, Isaacson J, Jackson RL, Murray E, Patick AK, Peng Q, Perros M, Pickford C, Wu H, Butler SL (2009) New small-molecule inhibitor class targeting human immunodeficiency virus type 1 virion maturation. Antimicrob Agents Chemother 53:5080-5087
        doi: 10.1128/AAC.00759-09

    8. Blair WS, Pickford C, Irving SL, Brown DG, Anderson M, Bazin R, Cao J, Ciaramella G, Isaacson J, Jackson L, Hunt R, Kjerrstrom A, Nieman JA, Patick AK, Perros M, Scott AD, Whitby K, Wu H, Butler SL (2010) HIV capsid is a tractable target for small molecule therapeutic intervention. PLoS Pathog 6:e1001220
        doi: 10.1371/journal.ppat.1001220

    9. Borsetti A, Ohagen A, Gottlinger HG (1998) The C-terminal half of the human immunodeficiency virus type 1 Gag precursor is sufficient for efficient particle assembly. J Virol 72:9313-9317

    10. Brass AL, Dykxhoorn DM, Benita Y, Yan N, Engelman A, Xavier RJ, Lieberman J, Elledge SJ (2008) Identification of host proteins required for HIV infection through a functional genomic screen. Science 319:921-926
        doi: 10.1126/science.1152725

    11. Briggs JA, Grunewald K, Glass B, Forster F, Krausslich HG, Fuller SD (2006) The mechanism of HIV-1 core assembly: insights from three-dimensional reconstructions of authentic virions. Structure 14:15-20
        doi: 10.1016/j.str.2005.09.010

    12. Briggs JA, Riches JD, Glass B, Bartonova V, Zanetti G, Krausslich HG (2009) Structure and assembly of immature HIV. Proc Natl Acad Sci USA 106:11090-11095
        doi: 10.1073/pnas.0903535106

    13. Buffone C, Schulte B, Opp S, Diaz-Griffero F (2015) Contribution of MxB oligomerization to HIV-1 capsid binding and restriction. J Virol 89:3285-3294
        doi: 10.1128/JVI.03730-14

    14. Buffone C, Martinez-Lopez A, Fricke T, Opp S, Severgnini M, Cifola I, Petiti L, Frabetti S, Skorupka K, Zadrozny KK, Ganser-Pornillos BK, Pornillos O, Di Nunzio F, Diaz-Griffero F (2018) Nup153 unlocks the nuclear pore complex for HIV-1 nuclear translocation in nondividing cells. J Virol 92:e00648-00618

    15. Bui KH, von Appen A, DiGuilio AL, Ori A, Sparks L, Mackmull MT, Bock T, Hagen W, Andres-Pons A, Glavy JS, Beck M (2013) Integrated structural analysis of the human nuclear pore complex scaffold. Cell 155:1233-1243
        doi: 10.1016/j.cell.2013.10.055

    16. Bukrinskaya A, Brichacek B, Mann A, Stevenson M (1998) Establishment of a functional human immunodeficiency virus type 1 (HIV-1) reverse transcription complex involves the cytoskeleton. J Exp Med 188:2113-2125
        doi: 10.1084/jem.188.11.2113

    17. Bukrinsky MI, Haggerty S, Dempsey MP, Sharova N, Adzhubel A, Spitz L, Lewis P, Goldfarb D, Emerman M, Stevenson M (1993) A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature 365:666-669
        doi: 10.1038/365666a0

    18. Burdick RC, Delviks-Frankenberry KA, Chen J, Janaka SK, Sastri J, Hu WS, Pathak VK (2017) Dynamics and regulation of nuclear import and nuclear movements of HIV-1 complexes. PLoS Pathog 13:e1006570
        doi: 10.1371/journal.ppat.1006570

    19. Busnadiego I, Kane M, Rihn SJ, Preugschas HF, Hughes J, Blanco-Melo D, Strouvelle VP, Zang TM, Willett BJ, Boutell C, Bieniasz PD, Wilson SJ (2014) Host and viral determinants of Mx2 antiretroviral activity. J Virol 88:7738-7752
        doi: 10.1128/JVI.00214-14

    20. Campbell EM, Hope TJ (2015) HIV-1 capsid: the multifaceted key player in HIV-1 infection. Nat Rev Microbiol 13:471-483
        doi: 10.1038/nrmicro3503

    21. Carlson LA, Briggs JA, Glass B, Riches JD, Simon MN, Johnson MC, Muller B, Grunewald K, Krausslich HG (2008) Three-dimensional analysis of budding sites and released virus suggests a revised model for HIV-1 morphogenesis. Cell Host Microbe 4:592-599
        doi: 10.1016/j.chom.2008.10.013

    22. Carnes SK, Sheehan JH, Aiken C (2018a) Inhibitors of the HIV-1 capsid, a target of opportunity. Curr Opin HIV AIDS 13:359-365
        doi: 10.1097/COH.0000000000000472

    23. Carnes SK, Zhou J, Aiken C (2018b) HIV-1 engages a dynein-dynactin-BICD2 complex for infection and transport to the nucleus. J Virol. https://doi.org/10.1128/JVI.00358-18:e00358-00318
        doi: 10.1128/JVI.00358-18:e00358-00318

    24. Chen NY, Zhou L, Gane PJ, Opp S, Ball NJ, Nicastro G, Zufferey M, Buffone C, Luban J, Selwood D, Diaz-Griffero F, Taylor I, Fassati A (2016) HIV-1 capsid is involved in post-nuclear entry steps. Retrovirology 13:28
        doi: 10.1186/s12977-016-0262-0

    25. Chin CR, Perreira JM, Savidis G, Portmann JM, Aker AM, Feeley EM, Smith MC, Brass AL (2015) Direct visualization of HIV-1 replication intermediates shows that capsid and CPSF6 modulate HIV-1 intra-nuclear invasion and integration. Cell Rep 13:1717-1731
        doi: 10.1016/j.celrep.2015.10.036

    26. De Iaco A, Luban J (2011) Inhibition of HIV-1 infection by TNPO3 depletion is determined by capsid and detectable after viral cDNA enters the nucleus. Retrovirology 8:98
        doi: 10.1186/1742-4690-8-98

    27. De Iaco A, Santoni F, Vannier A, Guipponi M, Antonarakis S, Luban J (2013) TNPO3 protects HIV-1 replication from CPSF6-mediated capsid stabilization in the host cell cytoplasm. Retrovirology 10:20
        doi: 10.1186/1742-4690-10-20

    28. Dharan A, Talley S, Tripathi A, Mamede JI, Majetschak M, Hope TJ, Campbell EM (2016) KIF5B and Nup358 cooperatively mediate the nuclear import of HIV-1 during infection. PLoS Pathog 12:e1005700
        doi: 10.1371/journal.ppat.1005700

    29. Dharan A, Opp S, Abdel-Rahim O, Keceli SK, Imam S, Diaz-Griffero F, Campbell EM (2017) Bicaudal D2 facilitates the cytoplasmic trafficking and nuclear import of HIV-1 genomes during infection. Proc Natl Acad Sci USA 114:E10707-E10716
        doi: 10.1073/pnas.1712033114

    30. Di Nunzio F, Danckaert A, Fricke T, Perez P, Fernandez J, Perret E, Roux P, Shorte S, Charneau P, Diaz-Griffero F, Arhel NJ (2012) Human nucleoporins promote HIV-1 docking at the nuclear pore, nuclear import and integration. PLoS ONE 7:e46037
        doi: 10.1371/journal.pone.0046037

    31. Di Nunzio F, Fricke T, Miccio A, Valle-Casuso JC, Perez P, Souque P, Rizzi E, Severgnini M, Mavilio F, Charneau P, Diaz-Griffero F (2013) Nup153 and Nup98 bind the HIV-1 core and contribute to the early steps of HIV-1 replication. Virology 440:8-18
        doi: 10.1016/j.virol.2013.02.008

    32. Dick RA, Zadrozny KK, Xu C, Schur FKM, Lyddon TD, Ricana CL, Wagner JM, Perilla JR, Ganser-Pornillos BK, Johnson MC, Pornillos O, Vogt VM (2018) Inositol phosphates are assembly co-factors for HIV-1. Nature 560:509-512
        doi: 10.1038/s41586-018-0396-4

    33. Fader LD, Bethell R, Bonneau P, Bos M, Bousquet Y, Cordingley MG, Coulombe R, Deroy P, Faucher AM, Gagnon A, Goudreau N, Grand-Maitre C, Guse I, Hucke O, Kawai SH, Lacoste JE, Landry S, Lemke CT, Malenfant E, Mason S, Morin S, O'Meara J, Simoneau B, Titolo S, Yoakim C (2011) Discovery of a 1, 5-dihydrobenzo[b][1, 4]diazepine-2, 4-dione series of inhibitors of HIV-1 capsid assembly. Bioorg Med Chem Lett 21:398-404
        doi: 10.1016/j.bmcl.2010.10.131

    34. Fassati A (2012) Multiple roles of the capsid protein in the early steps of HIV-1 infection. Virus Res 170:15-24
        doi: 10.1016/j.virusres.2012.09.012

    35. Fassati A, Goff SP (1999) Characterization of intracellular reverse transcription complexes of Moloney murine leukemia virus. J Virol 73:8919-8925

    36. Fassati A, Goff SP (2001) Characterization of intracellular reverse transcription complexes of human immunodeficiency virus type 1. J Virol 75:3626-3635
        doi: 10.1128/JVI.75.8.3626-3635.2001

    37. Fernandez J, Portilho DM, Danckaert A, Munier S, Becker A, Roux P, Zambo A, Shorte S, Jacob Y, Vidalain PO, Charneau P, Clavel F, Arhel NJ (2015) Microtubule-associated proteins 1 (MAP1) promote human immunodeficiency virus type Ⅰ (HIV-1) intracytoplasmic routing to the nucleus. J Biol Chem 290:4631-4646
        doi: 10.1074/jbc.M114.613133

    38. Fontana J, Keller PW, Urano E, Ablan SD, Steven AC, Freed EO (2016) Identification of an HIV-1 mutation in spacer peptide 1 that stabilizes the immature CA-SP1 lattice. J Virol 90:972-978
        doi: 10.1128/JVI.02204-15

    39. Francis AC, Melikyan GB (2018) Single HIV-1 imaging reveals progression of infection through CA-dependent steps of docking at the nuclear pore, uncoating, and nuclear transport. Cell Host Microbe 23:536-548e536
        doi: 10.1016/j.chom.2018.03.009

    40. Francis AC, Marin M, Shi J, Aiken C, Melikyan GB (2016) Time-resolved imaging of single HIV-1 uncoating in vitro and in living cells. PLoS Pathog 12:e1005709
        doi: 10.1371/journal.ppat.1005709

    41. Frank GA, Narayan K, Bess JW Jr, Del Prete GQ, Wu X, Moran A, Hartnell LM, Earl LA, Lifson JD, Subramaniam S (2015) Maturation of the HIV-1 core by a non-diffusional phase transition. Nat Commun 6:5854
        doi: 10.1038/ncomms6854

    42. Freed EO (2015) HIV-1 assembly, release and maturation. Nat Rev Microbiol 13:484-496
        doi: 10.1038/nrmicro3490

    43. Freed EO, Martin MA (1994) HIV-1 infection of non-dividing cells. Nature 369:107-108

    44. Freed EO, Englund G, Martin MA (1995) Role of the basic domain of human immunodeficiency virus type 1 matrix in macrophage infection. J Virol 69:3949-3954

    45. Freed EO, Englund G, Maldarelli F, Martin MA (1997) Phosphorylation of residue 131 of HIV-1 matrix is not required for macrophage infection. Cell 88:171-173 (discussion 173-174)

    46. Fribourgh JL, Nguyen HC, Matreyek KA, Alvarez FJD, Summers BJ, Dewdney TG, Aiken C, Zhang P, Engelman A, Xiong Y (2014) Structural insight into HIV-1 restriction by MxB. Cell Host Microbe 16:627-638
        doi: 10.1016/j.chom.2014.09.021

    47. Fricke T, Valle-Casuso JC, White TE, Brandariz-Nunez A, Bosche WJ, Reszka N, Gorelick R, Diaz-Griffero F (2013) The ability of TNPO3-depleted cells to inhibit HIV-1 infection requires CPSF6. Retrovirology 10:46
        doi: 10.1186/1742-4690-10-46

    48. Fricke T, White TE, Schulte B, de Souza Aranha Vieira DA, Dharan A, Campbell EM, Brandariz-Nunez A, Diaz-Griffero F (2014) MxB binds to the HIV-1 core and prevents the uncoating process of HIV-1. Retrovirology 11:68
        doi: 10.1186/s12977-014-0068-x

    49. Gallay P, Swingler S, Aiken C, Trono D (1995a) HIV-1 infection of nondividing cells: C-terminal tyrosine phosphorylation of the viral matrix protein is a key regulator. Cell 80:379-388
        doi: 10.1016/0092-8674(95)90488-3

    50. Gallay P, Swingler S, Song J, Bushman F, Trono D (1995b) HIV nuclear import is governed by the phosphotyrosine-mediated binding of matrix to the core domain of integrase. Cell 83:569-576
        doi: 10.1016/0092-8674(95)90097-7

    51. Gamble TR, Vajdos FF, Yoo S, Worthylake DK, Houseweart M, Sundquist WI, Hill CP (1996) Crystal structure of human cyclophilin A bound to the amino-terminal domain of HIV-1 capsid. Cell 87:1285-1294
        doi: 10.1016/S0092-8674(00)81823-1

    52. Gamble TR, Yoo S, Vajdos FF, von Schwedler UK, Worthylake DK, Wang H, McCutcheon JP, Sundquist WI, Hill CP (1997) Structure of the carboxyl-terminal dimerization domain of the HIV-1 capsid protein. Science 278:849-853
        doi: 10.1126/science.278.5339.849

    53. Ganser BK, Li S, Klishko VY, Finch JT, Sundquist WI (1999) Assembly and analysis of conical models for the HIV-1 core. Science 283:80-83
        doi: 10.1126/science.283.5398.80

    54. Gitti RK, Lee BM, Walker J, Summers MF, Yoo S, Sundquist WI (1996) Structure of the amino-terminal core domain of the HIV-1 capsid protein. Science 273:231-235
        doi: 10.1126/science.273.5272.231

    55. Goudreau N, Lemke CT, Faucher AM, Grand-Maitre C, Goulet S, Lacoste JE, Rancourt J, Malenfant E, Mercier JF, Titolo S, Mason SW (2013) Novel inhibitor binding site discovery on HIV-1 capsid N-terminal domain by NMR and X-ray crystallography. ACS Chem Biol 8:1074-1082
        doi: 10.1021/cb400075f

    56. Goujon C, Moncorge O, Bauby H, Doyle T, Ward CC, Schaller T, Hue S, Barclay WS, Schulz R, Malim MH (2013) Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection. Nature 502:559-562
        doi: 10.1038/nature12542

    57. Goujon C, Moncorge O, Bauby H, Doyle T, Barclay WS, Malim MH (2014) Transfer of the amino-terminal nuclear envelope targeting domain of human MX2 converts MX1 into an HIV-1 resistance factor. J Virol 88:9017-9026
        doi: 10.1128/JVI.01269-14

    58. Gres AT, Kirby KA, KewalRamani VN, Tanner JJ, Pornillos O, Sarafianos SG (2015) X-ray crystal structures of native HIV-1 capsid protein reveal conformational variability. Science 349:99-103
        doi: 10.1126/science.aaa5936

    59. Hu WS, Hughes SH (2012) HIV-1 reverse transcription. Cold Spring Harb Perspect Med 2:a006882

    60. Hulme AE, Perez O, Hope TJ (2011) Complementary assays reveal a relationship between HIV-1 uncoating and reverse transcription. Proc Natl Acad Sci USA 108:9975-9980
        doi: 10.1073/pnas.1014522108

    61. Hulme AE, Kelley Z, Foley D, Hope TJ (2015) Complementary assays reveal a low level of CA associated with viral complexes in the nuclei of HIV-1-infected cells. J Virol 89:5350-5361
        doi: 10.1128/JVI.00476-15

    62. Jacques DA, McEwan WA, Hilditch L, Price AJ, Towers GJ, James LC (2016) HIV-1 uses dynamic capsid pores to import nucleotides and fuel encapsidated DNA synthesis. Nature 536:349-353
        doi: 10.1038/nature19098

    63. Kane M, Yadav SS, Bitzegeio J, Kutluay SB, Zang T, Wilson SJ, Schoggins JW, Rice CM, Yamashita M, Hatziioannou T, Bieniasz PD (2013) MX2 is an interferon-induced inhibitor of HIV-1 infection. Nature 502:563-566
        doi: 10.1038/nature12653

    64. Kane M, Rebensburg SV, Takata MA, Zang TM, Yamashita M, Kvaratskhelia M, Bieniasz PD (2018) Nuclear pore heterogeneity influences HIV-1 infection and the antiviral activity of MX2. Elife 7:e35738
        doi: 10.7554/eLife.35738

    65. Keller PW, Adamson CS, Heymann JB, Freed EO, Steven AC (2011) HIV-1 maturation inhibitor bevirimat stabilizes the immature Gag lattice. J Virol 85:1420-1428
        doi: 10.1128/JVI.01926-10

    66. Keller PW, Huang RK, England MR, Waki K, Cheng N, Heymann JB, Craven RC, Freed EO, Steven AC (2013) A two-pronged structural analysis of retroviral maturation indicates that core formation proceeds by a disassembly-reassembly pathway rather than a displacive transition. J Virol 87:13655-13664
        doi: 10.1128/JVI.01408-13

    67. Kelly BN, Kyere S, Kinde I, Tang C, Howard BR, Robinson H, Sundquist WI, Summers MF, Hill CP (2007) Structure of the antiviral assembly inhibitor CAP-1 complex with the HIV-1 CA protein. J Mol Biol 373:355-366
        doi: 10.1016/j.jmb.2007.07.070

    68. Kim J, Tipper C, Sodroski J (2011) Role of TRIM5alpha RING domain E3 ubiquitin ligase activity in capsid disassembly, reverse transcription blockade, and restriction of simian immunodeficiency virus. J Virol 85:8116-8132
        doi: 10.1128/JVI.00341-11

    69. Knockenhauer KE, Schwartz TU (2016) The nuclear pore complex as a flexible and dynamic gate. Cell 164:1162-1171
        doi: 10.1016/j.cell.2016.01.034

    70. Koh Y, Wu X, Ferris AL, Matreyek KA, Smith SJ, Lee K, KewalRamani VN, Hughes SH, Engelman A (2013) Differential effects of human immunodeficiency virus type 1 capsid and cellular factors nucleoporin 153 and LEDGF/p75 on the efficiency and specificity of viral DNA integration. J Virol 87:648-658
        doi: 10.1128/JVI.01148-12

    71. Konig R, Zhou Y, Elleder D, Diamond TL, Bonamy GM, Irelan JT, Chiang CY, Tu BP, De Jesus PD, Lilley CE, Seidel S, Opaluch AM, Caldwell JS, Weitzman MD, Kuhen KL, Bandyopadhyay S, Ideker T, Orth AP, Miraglia LJ, Bushman FD, Young JA, Chanda SK (2008) Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication. Cell 135:49-60
        doi: 10.1016/j.cell.2008.07.032

    72. Krishnan L, Matreyek KA, Oztop I, Lee K, Tipper CH, Li X, Dar MJ, Kewalramani VN, Engelman A (2010) The requirement for cellular transportin 3 (TNPO3 or TRN-SR2) during infection maps to human immunodeficiency virus type 1 capsid and not integrase. J Virol 84:397-406
        doi: 10.1128/JVI.01899-09

    73. Kutluay SB, Perez-Caballero D, Bieniasz PD (2013) Fates of retroviral core components during unrestricted and TRIM5-restricted infection. PLoS Pathog 9:e1003214
        doi: 10.1371/journal.ppat.1003214

    74. Lahaye X, Gentili M, Silvin A, Conrad C, Picard L, Jouve M, Zueva E, Maurin M, Nadalin F, Knott GJ, Zhao B, Du F, Rio M, Amiel J, Fox AH, Li P, Etienne L, Bond CS, Colleaux L, Manel N (2018) NONO detects the nuclear HIV capsid to promote cGAS-mediated innate immune activation. Cell 175(488-501):e422

    75. Lee K, Ambrose Z, Martin TD, Oztop I, Mulky A, Julias JG, Vandegraaff N, Baumann JG, Wang R, Yuen W, Takemura T, Shelton K, Taniuchi I, Li Y, Sodroski J, Littman DR, Coffin JM, Hughes SH, Unutmaz D, Engelman A, KewalRamani VN (2010) Flexible use of nuclear import pathways by HIV-1. Cell Host Microbe 7:221-233
        doi: 10.1016/j.chom.2010.02.007

    76. Lee K, Mulky A, Yuen W, Martin TD, Meyerson NR, Choi L, Yu H, Sawyer SL, Kewalramani VN (2012) HIV-1 capsid-targeting domain of cleavage and polyadenylation specificity factor 6. J Virol 86:3851-3860
        doi: 10.1128/JVI.06607-11

    77. Lemke CT, Titolo S, von Schwedler U, Goudreau N, Mercier JF, Wardrop E, Faucher AM, Coulombe R, Banik SS, Fader L, Gagnon A, Kawai SH, Rancourt J, Tremblay M, Yoakim C, Simoneau B, Archambault J, Sundquist WI, Mason SW (2012) Distinct effects of two HIV-1 capsid assembly inhibitor families that bind the same site within the N-terminal domain of the viral CA protein. J Virol 86:6643-6655
        doi: 10.1128/JVI.00493-12

    78. Lemke CT, Titolo S, Goudreau N, Faucher AM, Mason SW, Bonneau P (2013) A novel inhibitor-binding site on the HIV-1 capsid N-terminal domain leads to improved crystallization via compound-mediated dimerization. Acta Crystallogr D Biol Crystallogr 69:1115-1123
        doi: 10.1107/S0907444913006409

    79. Li S, Hill CP, Sundquist WI, Finch JT (2000) Image reconstructions of helical assemblies of the HIV-1 CA protein. Nature 407:409-413
        doi: 10.1038/35030177

    80. Li F, Goila-Gaur R, Salzwedel K, Kilgore NR, Reddick M, Matallana C, Castillo A, Zoumplis D, Martin DE, Orenstein JM, Allaway GP, Freed EO, Wild CT (2003) PA-457: a potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing. Proc Natl Acad Sci USA 100:13555-13560
        doi: 10.1073/pnas.2234683100

    81. Lienlaf M, Hayashi F, Di Nunzio F, Tochio N, Kigawa T, Yokoyama S, Diaz-Griffero F (2011) Contribution of E3-ubiquitin ligase activity to HIV-1 restriction by TRIM5alpha(rh): structure of the RING domain of TRIM5alpha. J Virol 85:8725-8737
        doi: 10.1128/JVI.00497-11

    82. Lingappa JR, Reed JC, Tanaka M, Chutiraka K, Robinson BA (2014) How HIV-1 Gag assembles in cells: putting together pieces of the puzzle. Virus Res 193:89-107
        doi: 10.1016/j.virusres.2014.07.001

    83. Liu Z, Pan Q, Ding S, Qian J, Xu F, Zhou J, Cen S, Guo F, Liang C (2013) The interferon-inducible MxB protein inhibits HIV-1 infection. Cell Host Microbe 14:398-410
        doi: 10.1016/j.chom.2013.08.015

    84. Machara A, Lux V, Kozisek M, Grantz Saskova K, Stepanek O, Kotora M, Parkan K, Pavova M, Glass B, Sehr P, Lewis J, Muller B, Krausslich HG, Konvalinka J (2016) Specific inhibitors of HIV capsid assembly binding to the C-terminal domain of the capsid protein: evaluation of 2-arylquinazolines as potential antiviral compounds. J Med Chem 59:545-558
        doi: 10.1021/acs.jmedchem.5b01089

    85. Maertens GN, Cook NJ, Wang W, Hare S, Gupta SS, Oztop I, Lee K, Pye VE, Cosnefroy O, Snijders AP, KewalRamani VN, Fassati A, Engelman A, Cherepanov P (2014) Structural basis for nuclear import of splicing factors by human Transportin 3. Proc Natl Acad Sci USA 111:2728-2733
        doi: 10.1073/pnas.1320755111

    86. Malikov V, da Silva ES, Jovasevic V, Bennett G, de Souza Aranha Vieira DA, Schulte B, Diaz-Griffero F, Walsh D, Naghavi MH (2015) HIV-1 capsids bind and exploit the kinesin-1 adaptor FEZ1 for inward movement to the nucleus. Nat Commun 6:6660
        doi: 10.1038/ncomms7660

    87. Mallery DL, Marquez CL, McEwan WA, Dickson CF, Jacques DA, Anandapadamanaban M, Bichel K, Towers GJ, Saiardi A, Bocking T, James LC (2018) IP6 is an HIV pocket factor that prevents capsid collapse and promotes DNA synthesis. Elife 7:e35335
        doi: 10.7554/eLife.35335

    88. Matreyek KA, Engelman A (2011) The requirement for nucleoporin NUP153 during human immunodeficiency virus type 1 infection is determined by the viral capsid. J Virol 85:7818-7827
        doi: 10.1128/JVI.00325-11

    89. Matreyek KA, Yucel SS, Li X, Engelman A (2013) Nucleoporin NUP153 phenylalanine-glycine motifs engage a common binding pocket within the HIV-1 capsid protein to mediate lentiviral infectivity. PLoS Pathog 9:e1003693
        doi: 10.1371/journal.ppat.1003693

    90. Mattei S, Glass B, Hagen WJ, Krausslich HG, Briggs JA (2016a) The structure and flexibility of conical HIV-1 capsids determined within intact virions. Science 354:1434-1437
        doi: 10.1126/science.aah4972

    91. Mattei S, Schur FK, Briggs JA (2016b) Retrovirus maturation—an extraordinary structural transformation. Curr Opin Virol 18:27-35
        doi: 10.1016/j.coviro.2016.02.008

    92. Mattei S, Tan A, Glass B, Muller B, Krausslich HG, Briggs JAG (2018) High-resolution structures of HIV-1 Gag cleavage mutants determine structural switch for virus maturation. Proc Natl Acad Sci USA 115:E9401-E9410
        doi: 10.1073/pnas.1811237115

    93. McDonald D, Vodicka MA, Lucero G, Svitkina TM, Borisy GG, Emerman M, Hope TJ (2002) Visualization of the intracellular behavior of HIV in living cells. J Cell Biol 159:441-452
        doi: 10.1083/jcb.200203150

    94. Meng X, Zhao G, Yufenyuy E, Ke D, Ning J, Delucia M, Ahn J, Gronenborn AM, Aiken C, Zhang P (2012) Protease cleavage leads to formation of mature trimer interface in HIV-1 capsid. PLoS Pathog 8:e1002886
        doi: 10.1371/journal.ppat.1002886

    95. Miller MD, Farnet CM, Bushman FD (1997) Human immunodeficiency virus type 1 preintegration complexes: studies of organization and composition. J Virol 71:5382-5390

    96. Ning J, Erdemci-Tandogan G, Yufenyuy EL, Wagner J, Himes BA, Zhao G, Aiken C, Zandi R, Zhang P (2016) In vitro protease cleavage and computer simulations reveal the HIV-1 capsid maturation pathway. Nat Commun 7:13689
        doi: 10.1038/ncomms13689

    97. Novikova M, Adams LJ, Fontana J, Gres AT, Balasubramaniam M, Winkler DC, Kudchodkar SB, Soheilian F, Sarafianos SG, Steven AC, Freed EO (2018) Identification of a structural element in HIV-1 Gag required for virus particle assembly and maturation. MBio 9:e01567-01518

    98. Nowicka-Sans B, Protack T, Lin Z, Li Z, Zhang S, Sun Y, Samanta H, Terry B, Liu Z, Chen Y, Sin N, Sit SY, Swidorski JJ, Chen J, Venables BL, Healy M, Meanwell NA, Cockett M, Hanumegowda U, Regueiro-Ren A, Krystal M, Dicker IB (2016) Identification and characterization of BMS-955176, a second-generation HIV-1 maturation inhibitor with improved potency, antiviral spectrum, and Gag polymorphic coverage. Antimicrob Agents Chemother 60:3956-3969
        doi: 10.1128/AAC.02560-15

    99. Ono A, Ablan SD, Lockett SJ, Nagashima K, Freed EO (2004) Phosphatidylinositol (4, 5) bisphosphate regulates HIV-1 Gag targeting to the plasma membrane. Proc Natl Acad Sci USA 101:14889-14894
        doi: 10.1073/pnas.0405596101

    100. Pante N, Kann M (2002) Nuclear pore complex is able to transport macromolecules with diameters of about 39 nm. Mol Biol Cell 13:425-434
        doi: 10.1091/mbc.01-06-0308

    101. Peng K, Muranyi W, Glass B, Laketa V, Yant SR, Tsai L, Cihlar T, Muller B, Krausslich HG (2014) Quantitative microscopy of functional HIV post-entry complexes reveals association of replication with the viral capsid. Elife 3:e04114
        doi: 10.7554/eLife.04114

    102. Perez-Caballero D, Hatziioannou T, Zhang F, Cowan S, Bieniasz PD (2005) Restriction of human immunodeficiency virus type 1 by TRIM-CypA occurs with rapid kinetics and independently of cytoplasmic bodies, ubiquitin, and proteasome activity. J Virol 79:15567-15572
        doi: 10.1128/JVI.79.24.15567-15572.2005

    103. Perrier M, Bertine M, Le Hingrat Q, Joly V, Visseaux B, Collin G, Landman R, Yazdanpanah Y, Descamps D, Charpentier C (2017) Prevalence of gag mutations associated with in vitro resistance to capsid inhibitor GS-CA1 in HIV-1 antiretroviral-naive patients. J Antimicrob Chemother 72:2954-2955
        doi: 10.1093/jac/dkx208

    104. Pornillos O, Ganser-Pornillos BK, Kelly BN, Hua Y, Whitby FG, Stout CD, Sundquist WI, Hill CP, Yeager M (2009) X-ray structures of the hexameric building block of the HIV capsid. Cell 137:1282-1292
        doi: 10.1016/j.cell.2009.04.063

    105. Pornillos O, Ganser-Pornillos BK, Yeager M (2011) Atomic-level modelling of the HIV capsid. Nature 469:424-427
        doi: 10.1038/nature09640

    106. Price AJ, Jacques DA, McEwan WA, Fletcher AJ, Essig S, Chin JW, Halambage UD, Aiken C, James LC (2014) Host cofactors and pharmacologic ligands share an essential interface in HIV-1 capsid that is lost upon disassembly. PLoS Pathog 10:e1004459
        doi: 10.1371/journal.ppat.1004459

    107. Purdy MD, Shi D, Chrustowicz J, Hattne J, Gonen T, Yeager M (2018) MicroED structures of HIV-1 Gag CTD-SP1 reveal binding interactions with the maturation inhibitor bevirimat. Proc Natl Acad Sci USA 115:13258-13263
        doi: 10.1073/pnas.1806806115

    108. Saad JS, Miller J, Tai J, Kim A, Ghanam RH, Summers MF (2006) Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly. Proc Natl Acad Sci USA 103:11364-11369
        doi: 10.1073/pnas.0602818103

    109. Schulte B, Buffone C, Opp S, Di Nunzio F, De Souza Aranha Vieira DA, Brandariz-Nunez A, Diaz-Griffero F (2015) Restriction of HIV-1 requires the N-terminal region of MxB as a capsid-binding motif but not as a nuclear localization signal. J Virol 89:8599-8610
        doi: 10.1128/JVI.00753-15

    110. Schur FK, Hagen WJ, Rumlova M, Ruml T, Muller B, Krausslich HG, Briggs JA (2015) Structure of the immature HIV-1 capsid in intact virus particles at 8.8 A resolution. Nature 517:505-508
        doi: 10.1038/nature13838

    111. Schur FK, Obr M, Hagen WJ, Wan W, Jakobi AJ, Kirkpatrick JM, Sachse C, Krausslich HG, Briggs JA (2016) An atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly and maturation. Science 353:506-508
        doi: 10.1126/science.aaf9620

    112. Sowd GA, Serrao E, Wang H, Wang W, Fadel HJ, Poeschla EM, Engelman AN (2016) A critical role for alternative polyadenylation factor CPSF6 in targeting HIV-1 integration to transcriptionally active chromatin. Proc Natl Acad Sci USA 113:E1054-E1063
        doi: 10.1073/pnas.1524213113

    113. Spearman P (2016) HIV-1 Gag as an antiviral target: development of assembly and maturation inhibitors. Curr Top Med Chem 16:1154-1166

    114. Sticht J, Humbert M, Findlow S, Bodem J, Muller B, Dietrich U, Werner J, Krausslich HG (2005) A peptide inhibitor of HIV-1 assembly in vitro. Nat Struct Mol Biol 12:671-677
        doi: 10.1038/nsmb964

    115. Stremlau M, Owens CM, Perron MJ, Kiessling M, Autissier P, Sodroski J (2004) The cytoplasmic body component TRIM5alpha restricts HIV-1 infection in Old World monkeys. Nature 427:848-853
        doi: 10.1038/nature02343

    116. Stultz RD, Cenker JJ, McDonald D (2017) Imaging HIV-1 genomic DNA from entry through productive infection. J Virol 91:e00034-00017

    117. Sundquist WI, Krausslich HG (2012) HIV-1 assembly, budding, and maturation. Cold Spring Harb Perspect Med 2:a006924

    118. Tang C, Loeliger E, Kinde I, Kyere S, Mayo K, Barklis E, Sun Y, Huang M, Summers MF (2003) Antiviral inhibition of the HIV-1 capsid protein. J Mol Biol 327:1013-1020
        doi: 10.1016/S0022-2836(03)00289-4

    119. Tang C, Loeliger E, Luncsford P, Kinde I, Beckett D, Summers MF (2004) Entropic switch regulates myristate exposure in the HIV-1 matrix protein. Proc Natl Acad Sci USA 101:517-522
        doi: 10.1073/pnas.0305665101

    120. Tedbury PR, Freed EO (2015) HIV-1 gag: an emerging target for antiretroviral therapy. Curr Top Microbiol Immunol 389:171-201

    121. Ternois F, Sticht J, Duquerroy S, Krausslich HG, Rey FA (2005) The HIV-1 capsid protein C-terminal domain in complex with a virus assembly inhibitor. Nat Struct Mol Biol 12:678-682
        doi: 10.1038/nsmb967

    122. Tse WC, Link JO, Mulato A, Niedziela-Majka A, Rowe W, Somoza JR, Villasenor AG, Yant SR, Zhang JR, Zheng J (2017) Discovery of novel potent HIV capsid inhibitors with long-acting potential. In: Conference on retroviruses and opportunistic infections Abstract 38—new HIV drugs, formulations, combinations, and resistance

    123. Urano E, Ablan SD, Mandt R, Pauly GT, Sigano DM, Schneider JP, Martin DE, Nitz TJ, Wild CT, Freed EO (2016) Alkyl amine bevirimat derivatives are potent and broadly active HIV-1 maturation inhibitors. Antimicrob Agents Chemother 60:190-197
        doi: 10.1128/AAC.02121-15

    124. Valle-Casuso JC, Di Nunzio F, Yang Y, Reszka N, Lienlaf M, Arhel N, Perez P, Brass AL, Diaz-Griffero F (2012) TNPO3 is required for HIV-1 replication after nuclear import but prior to integration and binds the HIV-1 core. J Virol 86:5931-5936
        doi: 10.1128/JVI.00451-12

    125. Vollmer B, Lorenz M, Moreno-Andres D, Bodenhofer M, De Magistris P, Astrinidis SA, Schooley A, Flotenmeyer M, Leptihn S, Antonin W (2015) Nup153 recruits the Nup107-160 complex to the inner nuclear membrane for interphasic nuclear pore complex assembly. Dev Cell 33:717-728
        doi: 10.1016/j.devcel.2015.04.027

    126. von Schwedler U, Kornbluth RS, Trono D (1994) The nuclear localization signal of the matrix protein of human immunodeficiency virus type 1 allows the establishment of infection in macrophages and quiescent T lymphocytes. Proc Natl Acad Sci USA 91:6992-6996
        doi: 10.1073/pnas.91.15.6992

    127. von Schwedler UK, Stemmler TL, Klishko VY, Li S, Albertine KH, Davis DR, Sundquist WI (1998) Proteolytic refolding of the HIV-1 capsid protein amino-terminus facilitates viral core assembly. EMBO J 17:1555-1568
        doi: 10.1093/emboj/17.6.1555

    128. Wagner JM, Zadrozny KK, Chrustowicz J, Purdy MD, Yeager M, Ganser-Pornillos BK, Pornillos O (2016) Crystal structure of an HIV assembly and maturation switch. Elife 5:e17063
        doi: 10.7554/eLife.17063

    129. Wagner JM, Christensen DE, Bhattacharya A, Dawidziak DM, Roganowicz MD, Wan Y, Pumroy RA, Demeler B, Ivanov DN, Ganser-Pornillos BK, Sundquist WI, Pornillos O (2018) General model for retroviral capsid pattern recognition by TRIM5 proteins. J Virol 92:e01563-01517

    130. Waki K, Durell SR, Soheilian F, Nagashima K, Butler SL, Freed EO (2012) Structural and functional insights into the HIV-1 maturation inhibitor binding pocket. PLoS Pathog 8:e1002997
        doi: 10.1371/journal.ppat.1002997

    131. Walde S, Thakar K, Hutten S, Spillner C, Nath A, Rothbauer U, Wiemann S, Kehlenbach RH (2012) The nucleoporin Nup358/RanBP2 promotes nuclear import in a cargo- and transport receptor-specific manner. Traffic 13:218-233
        doi: 10.1111/j.1600-0854.2011.01302.x

    132. Walsh D, Naghavi MH (2019) Exploitation of cytoskeletal networks during early viral infection. Trends Microbiol 27:39-50
        doi: 10.1016/j.tim.2018.06.008

    133. Walther TC, Pickersgill HS, Cordes VC, Goldberg MW, Allen TD, Mattaj IW, Fornerod M (2002) The cytoplasmic filaments of the nuclear pore complex are dispensable for selective nuclear protein import. J Cell Biol 158:63-77
        doi: 10.1083/jcb.200202088

    134. Wang W, Zhou J, Halambage UD, Jurado KA, Jamin AV, Wang Y, Engelman AN, Aiken C (2017) Inhibition of HIV-1 maturation via small-molecule targeting of the amino-terminal domain in the viral capsid protein. J Virol 91:e02155-02116

    135. Woodward CL, Cheng SN, Jensen GJ (2015) Electron cryotomography studies of maturing HIV-1 particles reveal the assembly pathway of the viral core. J Virol 89:1267-1277
        doi: 10.1128/JVI.02997-14

    136. Wright ER, Schooler JB, Ding HJ, Kieffer C, Fillmore C, Sundquist WI, Jensen GJ (2007) Electron cryotomography of immature HIV-1 virions reveals the structure of the CA and SP1 Gag shells. EMBO J 26:2218-2226
        doi: 10.1038/sj.emboj.7601664

    137. Xu H, Franks T, Gibson G, Huber K, Rahm N, Strambio De Castillia C, Luban J, Aiken C, Watkins S, Sluis-Cremer N, Ambrose Z (2013) Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay. Retrovirology 10:70
        doi: 10.1186/1742-4690-10-70

    138. Yamashita M, Emerman M (2004) Capsid is a dominant determinant of retrovirus infectivity in nondividing cells. J Virol 78:5670-5678
        doi: 10.1128/JVI.78.11.5670-5678.2004

    139. Yamashita M, Engelman AN (2017) Capsid-dependent host factors in HIV-1 infection. Trends Microbiol 25:741-755
        doi: 10.1016/j.tim.2017.04.004

    140. Yamashita M, Perez O, Hope TJ, Emerman M (2007) Evidence for direct involvement of the capsid protein in HIV infection of nondividing cells. PLoS Pathog 3:1502-1510

    141. Yap MW, Dodding MP, Stoye JP (2006) Trim-cyclophilin A fusion proteins can restrict human immunodeficiency virus type 1 infection at two distinct phases in the viral life cycle. J Virol 80:4061-4067
        doi: 10.1128/JVI.80.8.4061-4067.2006

    142. Zhang H, Zhao Q, Bhattacharya S, Waheed AA, Tong X, Hong A, Heck S, Curreli F, Goger M, Cowburn D, Freed EO, Debnath AK (2008) A cell-penetrating helical peptide as a potential HIV-1 inhibitor. J Mol Biol 378:565-580
        doi: 10.1016/j.jmb.2008.02.066

    143. Zhang W, Cao S, Martin JL, Mueller JD, Mansky LM (2015) Morphology and ultrastructure of retrovirus particles. AIMS Biophys 2:343-369
        doi: 10.3934/biophy.2015.3.343

    144. Zhao G, Perilla JR, Yufenyuy EL, Meng X, Chen B, Ning J, Ahn J, Gronenborn AM, Schulten K, Aiken C, Zhang P (2013) Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics. Nature 497:643-646
        doi: 10.1038/nature12162

    145. Zhou J, Yuan X, Dismuke D, Forshey BM, Lundquist C, Lee KH, Aiken C, Chen CH (2004) Small-molecule inhibition of human immunodeficiency virus type 1 replication by specific targeting of the final step of virion maturation. J Virol 78:922-929
        doi: 10.1128/JVI.78.2.922-929.2004

    146. Zhou L, Sokolskaja E, Jolly C, James W, Cowley SA, Fassati A (2011) Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. PLoS Pathog 7:e1002194
        doi: 10.1371/journal.ppat.1002194

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    Multiple Roles of HIV-1 Capsid during the Virus Replication Cycle

      Corresponding author: Eric O. Freed, efreed@nih.gov
      Corresponding author: Ke Peng, pengke@wh.iov.cn
    • 1. Virus-Cell Interaction Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA
    • 2. State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China

    Abstract: Human immunodeficiency virus-1 capsid (HIV-1 CA) is involved in different stages of the viral replication cycle. During virion assembly, CA drives the formation of the hexameric lattice in immature viral particles, while in mature virions CA monomers assemble in cone-shaped cores surrounding the viral RNA genome and associated proteins. In addition to its functions in late stages of the viral replication cycle, CA plays key roles in a number of processes during early phases of HIV-1 infection including trafficking, uncoating, recognition by host cellular proteins and nuclear import of the viral preintegration complex. As a result of efficient cooperation of CA with other viral and cellular proteins, integration of the viral genetic material into the host genome, which is an essential step for productive viral infection, successfully occurs. In this review, we will summarize available data on CA functions in HIV-1 replication, describing in detail its roles in late and early phases of the viral replication cycle.