1887

Abstract

Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) is an accessory protein that interacts with a number of cellular and viral proteins. The functions of many of these interactions in the pathogenesis of HIV-1 have been identified. Deletion of the gene reduces the virulence of HIV-1 dramatically, indicating the importance of this protein for the virus. This review describes the current findings on several established functions of HIV-1 Vpr and some possible roles proposed for this protein. Because Vpr exploits cellular proteins and pathways to influence the biology of HIV-1, understanding the functions of Vpr usually involves the study of cellular pathways. Several functions of Vpr are attributed to the virion-incorporated protein, but some of them are attributed to the expression of Vpr in HIV-1-infected cells. The structure of Vpr may be key to understanding the variety of its interactions. Due to the critical role of Vpr in HIV-1 pathogenicity, study of the interactions between Vpr and cellular proteins may help us to understand the mechanism(s) of HIV-1 pathogenicity.

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2009-08-01
2024-04-16
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References

  1. Agostini I., Navarro J. M., Rey F., Bouhamdan M., Spire B., Vigne R., Sire J. 1996; The human immunodeficiency virus type 1 Vpr transactivator: cooperation with promoter-bound activator domains and binding to TFIIB. J Mol Biol 261:599–606 [CrossRef]
    [Google Scholar]
  2. Agostini I., Navarro J. M., Bouhamdan M., Willetts K., Rey F., Spire B., Vigne R., Pomerantz R., Sire J. 1999; The HIV-1 Vpr co-activator induces a conformational change in TFIIB. FEBS Lett 450:235–239 [CrossRef]
    [Google Scholar]
  3. Andersen J. L., Planelles V. 2005; The role of Vpr in HIV-1 pathogenesis. Curr HIV Res 3:43–51 [CrossRef]
    [Google Scholar]
  4. Andersen J. L., Le Rouzic E., Planelles V. 2008; HIV-1 Vpr: mechanisms of G2 arrest and apoptosis. Exp Mol Pathol 85:2–10 [CrossRef]
    [Google Scholar]
  5. Anderson J. L., Hope T. J. 2004; HIV accessory proteins and surviving the host cell. Curr HIV/AIDS Rep 1:47–53 [CrossRef]
    [Google Scholar]
  6. Arunagiri C., Macreadie I., Hewish D., Azad A. 1997; A C-terminal domain of HIV-1 accessory protein Vpr is involved in penetration, mitochondrial dysfunction and apoptosis of human CD4+ lymphocytes. Apoptosis 2:69–76 [CrossRef]
    [Google Scholar]
  7. Ayyavoo V., Muthumani K., Kudchodkar S., Zhang D., Ramanathan P., Dayes N. S., Kim J. J., Sin J. I., Montaner L. J., Weiner D. B. 2002; HIV-1 viral protein R compromises cellular function in vivo . Int Immunol 14:13–22 [CrossRef]
    [Google Scholar]
  8. Bachand F., Yao X. J., Hrimech M., Rougeau N., Cohen E. 1999; Incorporation of Vpr into human immunodeficiency virus type 1 requires a direct interaction with the p6 domain of the p55 Gag precursor. J Biol Chem 274:9083–9091 [CrossRef]
    [Google Scholar]
  9. Balasubramanyam A., Mersmann H., Jahoor F., Phillips T. M., Sekhar R. V., Schubert U., Brar B., Iyer D., Smith E. O. other authors 2007; Effects of transgenic expression of HIV-1 Vpr on lipid and energy metabolism in mice. Am J Physiol Endocrinol Metab 292:E40–E48
    [Google Scholar]
  10. Basanez G., Zimmerberg J. 2001; HIV and apoptosis: death and the mitochondrion. J Exp Med 193:F11–F14 [CrossRef]
    [Google Scholar]
  11. Basavapathruni A., Anderson K. S. 2007; Reverse transcription of the HIV-1 pandemic. FASEB J 21:3795–3808 [CrossRef]
    [Google Scholar]
  12. Belzile J. P., Duisit G., Rougeau N., Mercier J., Finzi A., Cohen E. A. 2007; HIV-1 Vpr-mediated G2 arrest involves the DDB1–CUL4AVPRBP E3 ubiquitin ligase. PLoS Pathog 3:E85 [CrossRef]
    [Google Scholar]
  13. Benko Z., Liang D., Agbottah E., Hou J., Taricani L., Young P. G., Bukrinsky M., Zhao R. Y. 2007; Antagonistic interaction of HIV-1 Vpr with Hsf-mediated cellular heat shock response and Hsp16 in fission yeast ( Schizosaccharomyces pombe ). Retrovirology 4:16 [CrossRef]
    [Google Scholar]
  14. Berkhout B., de Ronde A. 2004; APOBEC3G versus reverse transcriptase in the generation of HIV-1 drug-resistance mutations. AIDS 18:1861–1863 [CrossRef]
    [Google Scholar]
  15. Bouhamdan M., Benichou S., Rey F., Navarro J. M., Agostini I., Spire B., Camonis J., Slupphaug G., Vigne R. other authors 1996; Human immunodeficiency virus type 1 Vpr protein binds to the uracil DNA glycosylase DNA repair enzyme. J Virol 70:697–704
    [Google Scholar]
  16. Bouhamdan M., Xue Y. N., Baudat Y., Hu B., Sire J., Pomerantz R. J., Duan L. X. 1998; Diversity of HIV-1 Vpr interactions involves usage of the WXXF motif of host cell proteins. J Biol Chem 273:8009–8016 [CrossRef]
    [Google Scholar]
  17. Budihardjo I., Oliver H., Lutter M., Lue X., Wang X. 1999; Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol 15:269–290 [CrossRef]
    [Google Scholar]
  18. Chang L. J., Chen C. H., Urlacher V., Lee T. F. 2000; Differential apoptosis effects of primate lentiviral Vpr and Vpx in mammalian cells. J Biomed Sci 7:322–333 [CrossRef]
    [Google Scholar]
  19. Chang F., Re F., Sebastian S., Sazer S., Luban J. 2004; HIV-1 Vpr induces defects in mitosis, cytokinesis, nuclear structure, and centrosomes. Mol Biol Cell 15:1793–1801 [CrossRef]
    [Google Scholar]
  20. Chen R., Wang H., Mansky L. M. 2002; Roles of uracil–DNA glycosylase and dUTPase in virus replication. J Gen Virol 83:2339–2345
    [Google Scholar]
  21. Chen R., Le Rouzic E., Kearney J. A., Mansky L. M., Benichou S. 2004; Vpr-mediated incorporation of UNG2 into HIV-1 particles is required to modulate the virus mutation rate and for replication in macrophages. J Biol Chem 279:28419–28425 [CrossRef]
    [Google Scholar]
  22. Conti L., Matarrese P., Varano B., Gauzzi M. C., Sato A., Malorni W., Belardelli F., Gessani S. 2000; Dual role of the HIV-1 Vpr protein in the modulation of the apoptotic response of T cells. J Immun 165:3293–3300 [CrossRef]
    [Google Scholar]
  23. Csikasz-Nagy A., Battogtokh D., Chen K. C., Novak B., Tyson J. J. 2006; Analysis of a generic model of eukaryotic cell-cycle regulation. Biophys J 90:4361–4379 [CrossRef]
    [Google Scholar]
  24. de Noronha C. M., Sherman M. P., Lin H. W., Cavrois M. V., Moir R. D., Goldman R. D., Greene W. C. 2001; Dynamic disruptions in nuclear envelope architecture and integrity induced by HIV-1 Vpr. Science 294:1105–1108 [CrossRef]
    [Google Scholar]
  25. Elder R. T., Yu M., Chen M., Zhu X., Yanagida M., Zhao Y. 2001; HIV-1 Vpr induces cell cycle G2 arrest in fission yeast ( Schizosaccharomyces pombe ) through a pathway involving regulatory and catalytic subunits of PP2A and acting on both Wee1 and Cdc25. Virology 287:359–370 [CrossRef]
    [Google Scholar]
  26. Engler A., Stangler T., Willbold D. 2001; Solution structure of human immunodeficiency virus type 1 Vpr (13–33) peptide in micelles. Eur J Biochem 268:389–395 [CrossRef]
    [Google Scholar]
  27. Felzien L. K., Woffendin C., Hottiger M. O., Subbramanian R. A., Cohen E. A., Nabel G. J. 1998; HIV transcriptional activation by the accessory protein, VPR, is mediated by the p300 co-activator. Proc Natl Acad Sci U S A 95:5281–5286 [CrossRef]
    [Google Scholar]
  28. Gallay P., Stitt V., Mundy C., Oettinger M., Trono D. 1996; Role of the karyopherin pathway in human immunodeficiency virus type 1 nuclear import. J Virol 70:1027–1032
    [Google Scholar]
  29. Gallay P., Hope T., Chin D., Trono D. 1997; HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway. Proc Natl Acad Sci U S A 94:9825–9830 [CrossRef]
    [Google Scholar]
  30. Gao L., Balakrishnan M., Roques B. P., Bambara R. A. 2007; Insights into the multiple roles of pausing in HIV-1 reverse transcriptase-promoted strand transfers. J Biol Chem 282:6222–6231
    [Google Scholar]
  31. Giaccia A. J., Kastan M. B. 1998; The complexity of p53 modulation: emerging patterns from divergent signals. Genes Dev 12:2973–2983 [CrossRef]
    [Google Scholar]
  32. Gieffers C., Schleiffer A., Peters J.-M. 2000; Cullins and cell cycle control. Protoplasma 211:20–28 [CrossRef]
    [Google Scholar]
  33. Goh W. C., Rogel M. E., Kinsey M., Michael S. F., Fultz P. N., Nowak M. A., Hahn B. H., Emerman M. 1998; HIV-1 Vpr increases viral expression by manipulation of the cell cycle: a mechanism for selection of Vpr in vivo . Nat Med 4:65–71 [CrossRef]
    [Google Scholar]
  34. Goh W. C., Manel N., Emerman M. 2004; The human immunodeficiency virus Vpr protein binds Cdc25C: implications for G2 arrest. Virology 318:337–349 [CrossRef]
    [Google Scholar]
  35. Green D. R. 2000; Apoptotic pathways: paper wraps stone blunts scissors. Cell 102:1–4 [CrossRef]
    [Google Scholar]
  36. He J., Choe S., Walker R., Di Marzio P., Morgan D. O., Landau N. R. 1995; Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34cdc2 activity. J Virol 69:6705–6711
    [Google Scholar]
  37. Higa L. A., Zhang H. 2007; Stealing the spotlight: CUL4–DDB1 ubiquitin ligase docks WD40-repeat proteins to destroy. Cell Div 2:5 [CrossRef]
    [Google Scholar]
  38. Hrecka K., Gierszewska M., Srivastava S., Kozaczkiewicz L., Swanson S. K., Florens L., Washburn M. P., Skowronski J. 2007; Lentiviral Vpr usurps Cul4–DDB1[VprBP] E3 ubiquitin ligase to modulate cell cycle. Proc Natl Acad Sci U S A 104:11778–11783 [CrossRef]
    [Google Scholar]
  39. Huang M. B., Weeks O., Zhao L. J., Saltarelli M., Bond V. C. 2000; Effects of extracellular human immunodeficiency virus type 1 Vpr protein in primary rat cortical cell cultures. J Neurovirol 6:202–220 [CrossRef]
    [Google Scholar]
  40. Huard S., Elder R. T., Liang D., Li G., Zhao R. I. 2008; Human immunodeficiency virus type 1 Vpr induces cell cycle G2 arrest through Srk1/MK2-mediated phosphorylation of Cdc25. J Virol 82:2904–2917 [CrossRef]
    [Google Scholar]
  41. Jacotot E., Ravagnan L., Loeffler M., Ferri K. F., Vieira H. L., Zamzami N., Costantini P., Druillennec S., Hoebeke J. other authors 2000; The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore. J Exp Med 191:33–45 [CrossRef]
    [Google Scholar]
  42. Jacotot E., Ferri K. F., El Hamel C., Brenner C., Druillennec S., Hoebeke J., Rustin P., Métivier D., Lenoir C. other authors 2001; Control of mitochondrial membrane permeabilization by adenine nucleotide translocator interacting with HIV-1 viral protein R and Bcl-2. J Exp Med 193:509–519 [CrossRef]
    [Google Scholar]
  43. Jenkins Y., McEntee M., Weis K., Greene W. C. 1998; Characterization of HIV-1 Vpr nuclear import: analysis of signals and pathways. J Cell Biol 143:875–885 [CrossRef]
    [Google Scholar]
  44. Jin J., Arias E. E., Chen J., Harper J. W., Walter J. C. 2006; A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. Mol Cell 23:709–721 [CrossRef]
    [Google Scholar]
  45. Jowett J. B., Xie Y. M., Chen I. S. Y. 1999; The presence of human immunodeficiency virus type 1 Vpr correlates with a decrease in the frequency of mutations in a plasmid shuttle vector. J Virol 73:7132–7137
    [Google Scholar]
  46. Keele B. F., Giorgi E. E., Salazar-Gonzalez J. F., Decker J. M., Pham K. T., Salazar M. G., Sun C., Grayson T., Wang S. other authors 2008; Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A 105:7552–7557 [CrossRef]
    [Google Scholar]
  47. Kim H. E., Du F., Fang M., Wang X. 2005; Formation of apoptosome is initiated by cytochrome c -induced dATP hydrolysis and subsequent nucleotide exchange on Apaf-1. Proc Natl Acad Sci U S A 102:17545–17550 [CrossRef]
    [Google Scholar]
  48. Kino T., Chrousos G. P. 2004; Human immunodeficiency virus type-1 accessory protein Vpr: a causative agent of the AIDS-related insulin resistance/lipodystrophy syndrome?. Ann N Y Acad Sci 1024:153–167 [CrossRef]
    [Google Scholar]
  49. Kino T., Gragerov A., Slobodskaya O. 2002; Human immunodeficiency virus type 1 (HIV-1) accessory protein Vpr induces transcription of the HIV-1 and glucocorticoid-responsive promoters by binding directly to p300/CBP coactivators. J Virol 76:9724–9734 [CrossRef]
    [Google Scholar]
  50. Kino T., Gragerov A., Valentin A., Tsopanomihalou M., Ilyina-Gragerova G., Erwin-Cohen R., Chrousos G. P., Pavlakis G. N. 2005; Vpr protein of human immunodeficiency virus type 1 binds to 14-3-3 proteins and facilitates complex formation with Cdc25C: implications for cell cycle arrest. J Virol 79:2780–2787 [CrossRef]
    [Google Scholar]
  51. Kitayama H., Miura Y., Ando Y., Hoshino S., Ishizaka Y., Koyanagi Y. 2008; Human immunodeficiency virus type 1 Vpr inhibits axonal outgrowth through induction of mitochondrial dysfunction. J Virol 82:2528–2542 [CrossRef]
    [Google Scholar]
  52. Krylov D. M., Nasmyth K., Koonin E. V. 2003; Evolution of eukaryotic cell cycle regulation: stepwise addition of regulatory kinases and late advent of the CDKs. Curr Biol 13:173–177 [CrossRef]
    [Google Scholar]
  53. Lavallee C., Yao X. J., Ladha A., Gottlinger H., Haseltine W. A., Cohen E. A. 1994; Requirement of the Pr55gag precursor for incorporation of the Vpr product into human immunodeficiency virus type 1 viral particles. J Virol 68:1926–1934
    [Google Scholar]
  54. Le Rouzic E., Benichou S. 2005; The Vpr protein from HIV-1: distinct roles along the viral life cycle. Retrovirology 2:11 [CrossRef]
    [Google Scholar]
  55. Le Rouzic E., Mousnier A., Rustum C., Stutz F., Hallberg E., Dargemont C., Benichou S. 2002; Docking of HIV-1 Vpr to the nuclear envelope is mediated by the interaction with the nucleoporin hCG1. J Biol Chem 277:45091–45098 [CrossRef]
    [Google Scholar]
  56. Li Y., Zhang Z., Wakefield J. K., Kang S. M., Morrow C. D. 1997; Nucleotide substitutions within U5 are critical for efficient reverse transcription of human immunodeficiency virus type 1 with a primer binding site complementary to tRNAHis . J Virol 71:6315–6322
    [Google Scholar]
  57. Majumder B., Venkatachari N. J., O'Leary S., Ayyavoo V. 2008; Infection with Vpr-positive human immunodeficiency virus type 1 impairs NK cell function indirectly through cytokine dysregulation of infected target cells. J Virol 82:7189–7200 [CrossRef]
    [Google Scholar]
  58. Mansky L. M. 1996; The mutation rate of human immunodeficiency virus type 1 is influenced by the vpr gene. Virology 222:391–400 [CrossRef]
    [Google Scholar]
  59. Mansky L. M., Preveral S., Selig L., Benarous R., Benichou S. 2000; The interaction of Vpr with uracil DNA glycosylase modulates the human immunodeficiency virus type 1 in vivo mutation rate. J Virol 74:7039–7047 [CrossRef]
    [Google Scholar]
  60. Moon H. S., Yang J. S. 2006; Role of HIV Vpr as a regulator of apoptosis and an effector on bystander cells. Mol Cells 21:7–20
    [Google Scholar]
  61. Müller B., Tessmer U., Schubert U., Kräusslich H. G. 2000; Human immunodeficiency virus type 1 Vpr protein is incorporated into the virion in significantly smaller amounts than Gag and is phosphorylated in infected cells. J Virol 74:9727–9731 [CrossRef]
    [Google Scholar]
  62. Muthumani K., Kudchodkar S., Papasavvas E., Montaner L. J., Weiner D. B., Ayyavoo V. 2000; HIV-1 Vpr regulates expression of β chemokines in human primary lymphocytes and macrophages. J Leukoc Biol 68:366–372
    [Google Scholar]
  63. Muthumani K., Hwang D. S., Dayes N. S., Kim J. J., Weiner D. B. 2002a; The HIV-1 accessory gene vpr can inhibit antigen-specific immune function. DNA Cell Biol 21:689–695 [CrossRef]
    [Google Scholar]
  64. Muthumani K., Hwang D. S., Desai B. M., Zhang D., Dayes N. S., Green D. R., Weiner D. B. 2002b; HIV-1 Vpr induces apoptosis through caspase 9 in T cells and peripheral blood mononuclear cells. J Biol Chem 277:37820–37831 [CrossRef]
    [Google Scholar]
  65. Muthumani K., Desai B. M., Hwang D. S., Choo A. Y., Laddy D. J., Thieu K. P., Rao R. G., Weiner D. B. 2004a; HIV-1 Vpr and anti-inflammatory activity. DNA Cell Biol 23:239–247 [CrossRef]
    [Google Scholar]
  66. Muthumani K., Hwang D. S., Choo A. Y., Mayilvahanan S., Dayes N. S., Thieu K. P., Weiner D. B. 2004b; HIV-1 Vpr inhibits the maturation and activation of macrophages and dendritic cells in vitro . Int Immunol 17:103–116 [CrossRef]
    [Google Scholar]
  67. Muthumani K., Choo A. Y., Hwang D. S., Dayes N. S., Chattergoon M., Mayilvahanan S., Thieu K. P., Buckley P. T., Emmanuel J. other authors 2005; HIV-1 viral protein-R (Vpr) protects against lethal superantigen challenge while maintaining homeostatic T cell levels in vivo . Mol Ther 12:910–921 [CrossRef]
    [Google Scholar]
  68. Muthumani K., Choo A. Y., Zong W. X., Madesh M., Hwang D. S., Premkumar A., Thieu K. P., Emmanuel J., Kumar S. other authors 2006; The HIV-1 Vpr and glucocorticoid receptor complex is a gain-of-function interaction that prevents the nuclear localization of PARP-1. Nat Cell Biol 8:170–179 [CrossRef]
    [Google Scholar]
  69. Nitahara-Kasahara Y., Kamata M., Yamamoto T., Zhang X., Miyamoto Y., Muneta K., Iijima S., Yoneda Y., Tsunetsugu-Yokota Y., Aida Y. 2007; A novel nuclear import of Vpr promoted by importin α is crucial for HIV-1 replication in macrophages. J Virol 81:5284–5293 [CrossRef]
    [Google Scholar]
  70. Pauls E., Senserrich J., Clotet B., Este J. A. 2006; Inhibition of HIV-1 replication by RNA interference of p53 expression. J Leukoc Biol 80:659–667 [CrossRef]
    [Google Scholar]
  71. Piller S. C., Jans P., Gage P. W., Jans D. A. 1998; Extracellular HIV-1 virus protein R causes a large inward current and cell death in cultured hippocampal neurons: implications for AIDS pathology. Proc Natl Acad Sci U S A 95:4595–4600 [CrossRef]
    [Google Scholar]
  72. Piller S. C., Ewart G. D., Jans D. A., Gage P. W., Cox G. B. 1999; The amino-terminal region of Vpr from human immunodeficiency virus type 1 forms ion channels and kills neurons. J Virol 73:4230–4238
    [Google Scholar]
  73. Poon B., Chang M. A., Chen I. S. Y. 2007; Vpr is required for efficient Nef expression from unintegrated HIV-1 DNA. J Virol 81:10515–10523 [CrossRef]
    [Google Scholar]
  74. Priet S., Navarro J. M., Gros N., Querat G., Sire J. 2003; Functional role of HIV-1 virion-associated uracil DNA glycosylase 2 in the correction of G : U mispairs to G : C pairs. J Biol Chem 278:4566–4571 [CrossRef]
    [Google Scholar]
  75. Ramanathan M. P., Curley E., III, Su M., Chambers J. A., Weiner D. B. 2002; Carboxyl terminus of hVIP/mov34 is critical for HIV-1-Vpr interaction and glucocorticoid-mediated signaling. J Biol Chem 277:47854–47860 [CrossRef]
    [Google Scholar]
  76. Rialland M., Sola F., Santocanale C. 2002; Essential role of human CDT1 in DNA replication and chromatin licensing. J Cell Sci 115:1435–1440
    [Google Scholar]
  77. Rogel M. E., Wu L. I., Emerman M. 1995; The human immunodeficiency virus type 1 vpr gene prevents cell proliferation during chronic infection. J Virol 69:882–888
    [Google Scholar]
  78. Rom I., Deshmane S. L., Mukerjee R., Khalili K., Amini S., Sawaya B. E. 2009; HIV-1 Vpr deregulates calcium secretion in neural cells. Brain Res 1275:81–86 [CrossRef]
    [Google Scholar]
  79. Roumier T., Vieira H. L., Castedo M., Ferri K. F., Boya P., Andreau K., Druillennec S., Joza N., Penninger J. M. other authors 2002; The C-terminal moiety of HIV-1 Vpr induces cell death via a caspase-independent mitochondrial pathway. Cell Death Differ 9:1212–1219 [CrossRef]
    [Google Scholar]
  80. Sawaya B. E., Khalili K., Mercer W. E., Denisova L., Amini S. 1998; Cooperative actions of HIV-1 Vpr and p53 modulate viral gene transcription. J Biol Chem 273:20052–20057 [CrossRef]
    [Google Scholar]
  81. Sawaya B. E., Khalili K., Gordon J., Taube R., Amini S. 2000; Cooperative interaction between HIV-1 regulatory proteins Tat and Vpr modulates transcription of the viral genome. J Biol Chem 275:35209–35214 [CrossRef]
    [Google Scholar]
  82. Schang L. M. 2003; The cell cycle, cyclin-dependent kinases, and viral infections: new horizons and unexpected connections. Prog Cell Cycle Res 5:103–124
    [Google Scholar]
  83. Shrivastav S., Kino T., Cunningham T., Ichijo T., Schubert U., Heinklein P., Chrousos G. P., Kopp J. B. 2008; Human immunodeficiency virus (HIV)-1 viral protein R suppresses transcriptional activity of peroxisome proliferator-activated receptor γ and inhibits adipocyte differentiation: implications for HIV-associated lipodystrophy. Mol Endocrinol 22:234–247 [CrossRef]
    [Google Scholar]
  84. Somasundaran M., Sharkey M., Brichacek B., Luzuriaga K., Emerman M., Sullivan J. L., Stevenson M. 2002; Evidence for a cytopathogenicity determinant in HIV-1 Vpr. Proc Natl Acad Sci U S A 99:9503–9508 [CrossRef]
    [Google Scholar]
  85. Srinivasan A., Ayyavoo V., Mahalingam S., Kannan A., Boyd A., Datta D., Kalyanaraman V. S., Cristillo A., Collman R. G. other authors 2008; A comprehensive analysis of the naturally occurring polymorphisms in HIV-1 Vpr: potential impact on CTL epitopes. Virol J 5:99 [CrossRef]
    [Google Scholar]
  86. Stark L. A., Hay R. T. 1998; Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) interacts with Lys-tRNA synthetase: implications for priming of HIV-1 reverse transcription. J Virol 72:3037–3044
    [Google Scholar]
  87. Stewart S. A., Poon B., Jowett J. B. M., Xie Y., Chen I. S. Y. 1999; Lentiviral delivery of HIV-1 Vpr protein induces apoptosis in transformed cells. Proc Natl Acad Sci U S A 96:12039–12043 [CrossRef]
    [Google Scholar]
  88. Sun Y., Pinchuk L. M., Agy M. B., Clark E. A. 1997; Nuclear import of HIV-1 DNA in resting CD4+ T cells requires a cyclosporin A-sensitive pathway. J Immun 158:512–517
    [Google Scholar]
  89. Suzuki T., Yamamoto N., Nonaka M., Hashimoto Y., Matsuda G., Takeshima S. N., Matsuyama M., Igarashi T., Miura T. other authors 2009; Inhibition of human immunodeficiency virus type 1 (HIV-1) nuclear import via Vpr–importin α interactions as a novel HIV-1 therapy. Biochem Biophys Res Commun 380:838–843 [CrossRef]
    [Google Scholar]
  90. Tungaturthi P. K., Sawaya B. E., Ayyavoo V., Murali R., Srinivasan A. 2004; HIV-1 Vpr: genetic diversity and functional features from the perspective of structure. DNA Cell Biol 23:207–222 [CrossRef]
    [Google Scholar]
  91. Vafiadaki E., Sanoudou D., Arvanitis D. A., Catino D. H., Kranias E. G., Kontrogianni-Konstantopoulos A. 2006; Phospholamban interacts with HAX-1, a mitochondrial protein with anti-apoptotic function. J Mol Biol 367:65–79
    [Google Scholar]
  92. Vafiadaki E., Arvanitis D. A., Pagakis S. N., Papalouka V., Sanoudou D., Kontrogianni-Konstantopoulos A., Kranias E. G. 2009; The anti-apoptotic protein HAX-1 interacts with SERCA2 and regulates its protein levels to promote cell survival. Mol Biol Cell 20:306–318 [CrossRef]
    [Google Scholar]
  93. Varin A., Decrion A. Z., Sabbah E., Quivy V., Sire J., Lint C. V., Roques B. P., Aggarwal B. B., Herbein G. 2005; Synthetic Vpr protein activates activator protein-1, c-jun N-terminal kinase, and NF- κ B and stimulates HIV-1 transcription in promonocytic cells and primary macrophages. J Biol Chem 280:42557–42567 [CrossRef]
    [Google Scholar]
  94. Vodicka M. A., Koepp D. M., Silver P. M., Emerman M. 1998; HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection. Genes Dev 12:175–185 [CrossRef]
    [Google Scholar]
  95. Wang L., Mukherjee S., Jia F., Narayan O., Zhao L. J. 1995; Interaction of virion protein Vpr of human immunodeficiency virus type 1 with cellular transcription factor Sp1 and trans-activation of viral long terminal repeat. J Biol Chem 270:25564–25569 [CrossRef]
    [Google Scholar]
  96. Wang L., Mukherjee S., Narayan O., Zhao L. J. 1996; Characterization of a leucine-zipper-like domain in Vpr protein of human immunodeficiency virus type 1. Gene 178:7–13 [CrossRef]
    [Google Scholar]
  97. Wang J., Shackelford J. M., Selliah N., Shivers D. K., O'Neill E., Garcia J. V., Muthumani K., Weiner D., Yu X. F. other authors 2008; The HIV-1 Vif protein mediates degradation of Vpr and reduces Vpr-induced cell cycle arrest. DNA Cell Biol 27:267–277 [CrossRef]
    [Google Scholar]
  98. Warbrick E., Fantes P. A. 1988; A conserved eukaryotic cell cycle control. Bioessays 8:202–204 [CrossRef]
    [Google Scholar]
  99. Wen X., Duus K. M., Friedrich T. D., de Noronha C. M. C. 2007; The HIV1 protein Vpr acts to promote G2 cell cycle arrest by engaging a DDB1 and cullin4A-containing ubiquitin ligase complex using VprBP/DCAF1 as an adaptor. J Biol Chem 282:27046–27057 [CrossRef]
    [Google Scholar]
  100. Withers-Ward E. S., Jowett J. B. M., Stewart S. A., Xie Y. M., Garfinkel A., Shibagaki Y., Chow S. A., Shah N., Hanaoka F. other authors 1997; Human immunodeficiency virus type 1 Vpr interacts with HHR23A, a cellular protein implicated in nucleotide excision DNA repair. J Virol 71:9732–9742
    [Google Scholar]
  101. Xiao Y., Chen G., Richard J., Rougeau N., Li H., Seidah N. G., Cohen E. A. 2008; Cell-surface processing of extracellular human immunodeficiency virus type 1 Vpr by proprotein convertases. Virology 372:384–397 [CrossRef]
    [Google Scholar]
  102. Yao X. J., Lemay J., Rougeau N., Clement M., Kurtz S., Belhumeur P., Cohen E. A. 2002; Genetic selection of peptide inhibitors of human immunodeficiency virus type 1 Vpr. J Biol Chem 277:48816–48826 [CrossRef]
    [Google Scholar]
  103. Yedavalli V. S. R. K., Shih H. M., Chiang Y. P., Lu C. Y., Chang L. Y., Chen M. Y., Chuang C. Y., Dayton A. I., Jeang K. T., Huang L. M. 2005; Human immunodeficiency virus type 1 Vpr interacts with antiapoptotic mitochondrial protein HAX-1. J Virol 79:13735–13746 [CrossRef]
    [Google Scholar]
  104. Zeitler B., Weis K. 2004; The FG-repeat asymmetry of the nuclear pore complex is dispensable for bulk nucleocytoplasmic transport in vivo . J Cell Biol 167:583–590 [CrossRef]
    [Google Scholar]
  105. Zhao R. Y., Bukrinsky M., Elder R. T. 2005; HIV-1 viral protein R (Vpr) & host cellular responses. Indian J Med Res 121:270–286
    [Google Scholar]
  106. Zhu Y., Gelbard H. A., Roshal M., Pursell S., Jamieson B. D., Planelles V. 2001; Comparison of cell cycle arrest, transactivation, and apoptosis induced by the simian immunodeficiency virus SIVagm and human immunodeficiency virus type 1 vpr genes. J Virol 75:3791–3801 [CrossRef]
    [Google Scholar]
  107. Zhu Y., Roshal M., Li F., Blackett J., Planelles V. 2003; Upregulation of survivin by HIV-1 Vpr. Apoptosis 8:71–79 [CrossRef]
    [Google Scholar]
  108. Zou H., Yang R., Hao J., Wang J., Sun C., Fesik S. W., Wu J. C., Tomaselli K. J., Armstrong R. C. 2003; Regulation of the Apaf-1/caspase-9 apoptosome by caspase-3 and XIAP. J Biol Chem 278:8091–8098 [CrossRef]
    [Google Scholar]
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