Roles of Vpr and Vpx in modulating the virus-host cell relationship

Molecular Aspects of Medicine

Volumn 31, Issue 5, 2010, Pages 398-406

  Planelles, Vicente ^a   Barker, Edward ^b  

^a UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^b RUSH UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

ATR; Cell cycle; HIV; Ubiquitin ligase; Vpr; Vpx

Indexed keywords

UBIQUITIN PROTEIN LIGASE; UNCLASSIFIED DRUG; VIRUS PROTEIN; VPR PROTEIN; VPX PROTEIN;

APOPTOSIS; CELL CYCLE ARREST; GENOTOXICITY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; NONHUMAN; PARALOGY; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; VIRUS CELL INTERACTION; VIRUS DNA CELL DNA INTERACTION; VIRUS REPLICATION;

APOPTOSIS; CELL CYCLE; DNA DAMAGE; HOST-PATHOGEN INTERACTIONS; HUMANS; SIMIAN IMMUNODEFICIENCY VIRUS; VIRAL REGULATORY AND ACCESSORY PROTEINS; VPR GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS;

SIMIAN IMMUNODEFICIENCY VIRUS;

EID: 77958462850     PISSN: 00982997     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.mam.2010.05.002     Document Type: Review

References (97)

1. Andersen J.L., DeHart J.L., Zimmerman E.S., Ardon O., Kim B., Jacquot G., Benichou S., Planelles V. HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. PLoS Pathog. 2006, 2(12):e127.
2. Andersen J.L., Zimmerman E.S., DeHart J.L., Murala S., Ardon O., Blackett J., Chen J., Planelles V. ATR and GADD45alpha mediate HIV-1 Vpr-induced apoptosis. Cell Death Differ. 2005, 12(4):326-334.
3. Angers S., Li T., Yi X., MacCoss M.J., Moon R.T., Zheng N. Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery. Nature 2006, 443(7111):590-593.
4. Bahram S., Bresnahan M., Geraghty D.E., Spies T. A second lineage of mammalian major histocompatibility complex class I genes. Proc. Natl. Acad. Sci. USA 1994, 91(14):6259-6263.
5. Baines C.P., Kaiser R.A., Purcell N.H., Blair N.S., Osinska H., Hambleton M.A., Brunskill E.W., Sayen M.R., Gottlieb R.A., Dorn G.W., Robbins J., Molkentin J.D. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 2005, 434(7033):658-662.
6. Bauer S., Groh V., Wu J., Steinle A., Phillips J.H., Lanier L.L., Spies T. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 1999, 285(5428):727-729.
7. Belzile J.P., Duisit G., Rougeau N., Mercier J., Finzi A., Cohen E.A. HIV-1 Vpr-mediated G2 arrest involves the DDB1-CUL4A(VPRBP) E3 ubiquitin ligase. PLoS Pathog. 2007, 3(7):e85.
8. Belzile, J.P., Richard, J., Rougeau, N., Xiao, Y., Cohen, E.A., 2010. HIV-1 Vpr induces the K48-linked polyubiquitination and proteasomal degradation of target cellular proteins to activate ATR and promote G2 arrest. J. Virol.
9. Bryceson Y.T., Ljunggren H.G., Long E.O. Minimal requirement for induction of natural cytotoxicity and intersection of activation signals by inhibitory receptors. Blood 2009, 114(13):2657-2666.
10. Bryceson Y.T., March M.E., Barber D.F., Ljunggren H.G., Long E.O. Cytolytic granule polarization and degranulation controlled by different receptors in resting NK cells. J. Exp. Med. 2005, 202(7):1001-1012.
11. Bryceson Y.T., March M.E., Ljunggren H.G., Long E.O. Activation, coactivation, and costimulation of resting human natural killer cells. Immunol. Rev. 2006, 214:73-91.
12. Bryceson Y.T., March M.E., Ljunggren H.G., Long E.O. Synergy among receptors on resting NK cells for the activation of natural cytotoxicity and cytokine secretion. Blood 2006, 107(1):159-166.
13. Cerboni C., Neri F., Casartelli N., Zingoni A., Cosman D., Rossi P., Santoni A., Doria M. Human immunodeficiency virus 1 Nef protein downmodulates the ligands of the activating receptor NKG2D and inhibits natural killer cell-mediated cytotoxicity. J. Gen. Virol. 2007, 88(Pt 1):242-250.
14. Cimprich K.A., Cortez D. ATR: an essential regulator of genome integrity. Nat. Rev. Mol. Cell Biol. 2008, 9(8):616-627.
15. Coeytaux E., Coulaud D., Le Cam E., Danos O., Kichler A. The cationic amphipathic alpha-helix of HIV-1 viral protein R (Vpr) binds to nucleic acids, permeabilizes membranes, and efficiently transfects cells. J. Biol. Chem. 2003, 278(20):18110-18116.
16. Cosman D., Mullberg J., Sutherland C.L., Chin W., Armitage R., Fanslow W., Kubin M., Chalupny N.J. ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor. Immunity 2001, 14(2):123-133.
17. DeHart J.L., Planelles V. Human immunodeficiency virus type 1 vpr links proteasomal degradation and checkpoint activation. J. Virol. 2008, 82(3):1066-1072.
18. DeHart J.L., Zimmerman E.S., Ardon O., Monteiro-Filho C.M., Arganaraz E.R., Planelles V. HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. Virol. J. 2007, 4(1):57.
19. Fletcher T.M., Brichacek B., Sharova N., Newman M.A., Stivahtis G., Sharp P.M., Emerman M., Hahn B.H., Stevenson M. Nuclear import and cell cycle arrest functions of the HIV-1 Vpr protein are encoded by two separate genes in HIV-2/SIV(SM). EMBO J. 1996, 15(22):6155-6165.
20. Fogli M., Mavilio D., Brunetta E., Varchetta S., Ata K., Roby G., Kovacs C., Follmann D., Pende D., Ward J., Barker E., Marcenaro E., Moretta A., Fauci A.S. Lysis of endogenously infected CD4+ T cell blasts by rIL-2 activated autologous natural killer cells from HIV-infected viremic individuals. PLoS Pathog. 2008, 4(7):e1000101.
21. Fritz J.V., Didier P., Clamme J.P., Schaub E., Muriaux D., Cabanne C., Morellet N., Bouaziz S., Darlix J.L., Mely Y., de Rocquigny H. Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging. Retrovirology 2008, 5:87.
22. Fujita M., Otsuka M., Miyoshi M., Khamsri B., Nomaguchi M., Adachi A. Vpx is critical for reverse transcription of the human immunodeficiency virus type 2 genome in macrophages. J. Virol. 2008, 82(15):7752-7756.
23. Gartner S., Markovits P., Markovitz D.M., Kaplan M.H., Gallo R.C., Popovic M. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 1986, 233(4760):215-219.
24. Gasser S., Orsulic S., Brown E.J., Raulet D.H. The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature 2005, 436(7054):1186-1190.
25. Ghorpade A., Nukuna A., Che M., Haggerty S., Persidsky Y., Carter E., Carhart L., Shafer L., Gendelman H.E. Human immunodeficiency virus neurotropism: an analysis of viral replication and cytopathicity for divergent strains in monocytes and microglia. J. Virol. 1998, 72(4):3340-3350.
26. Goh W.C., Rogel M.E., Kinsey C.M., Michael S.F., Fultz P.N., Nowak M.A., Hahn B.H., Emerman M. HIV-1 Vpr increases viral expression by manipulation of the cell cycle: a mechanism for selection of Vpr in vivo. Nat. Med. 1998, 4(1):65-71.
27. Gorry P.R., Churchill M., Crowe S.M., Cunningham A.L., Gabuzda D. Pathogenesis of macrophage tropic HIV-1. Curr. HIV Res. 2005, 3(1):53-60.
28. Goujon C., Riviere L., Jarrosson-Wuilleme L., Bernaud J., Rigal D., Darlix J.L., Cimarelli A. SIVSM/HIV-2 Vpx proteins promote retroviral escape from a proteasome-dependent restriction pathway present in human dendritic cells. Retrovirology 2007, 4:2.
29. Groh V., Steinle A., Bauer S., Spies T. Recognition of stress-induced MHC molecules by intestinal epithelial gammadelta T cells. Science 1998, 279(5357):1737-1740.
30. Guerra N., Tan Y.X., Joncker N.T., Choy A., Gallardo F., Xiong N., Knoblaugh S., Cado D., Greenberg N.R., Raulet D.H. NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy. Immunity 2008, 28(4):571-580.
31. Guyader M., Emerman M., Montagnier L., Peden K. VPX mutants of HIV-2 are infectious in established cell lines but display a severe defect in peripheral blood lymphocytes. EMBO J. 1989, 8(4):1169-1175.
32. Hattori N., Michaels F., Fargnoli K., Marcon L., Gallo R.C., Franchini G. The human immunodeficiency virus type 2 vpr gene is essential for productive infection of human macrophages. Proc. Natl. Acad. Sci. USA 1990, 87(20):8080-8084.
33. He J., Choe S., Walker R., Di Marzio P., Morgan D.O., Landau N.R. 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. 1995, 69(11):6705-6711.
34. He Y.J., McCall C.M., Hu J., Zeng Y., Xiong Y. DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases. Genes Dev. 2006, 20(21):2949-2954.
35. Higa L.A., Mihaylov I.S., Banks D.P., Zheng J., Zhang H. Radiation-mediated proteolysis of CDT 1 by CUL4-ROC1 and CSN complexes constitutes a new checkpoint. Nat. Cell Biol. 2003, 5(11):1008-1015.
36. Higa L.A., Wu M., Ye T., Kobayashi R., Sun H., Zhang H. CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation. Nat. Cell Biol. 2006, 8(11):1277-1283.
37. Higa L.A., Yang X., Zheng J., Banks D., Wu M., Ghosh P., Sun H., Zhang H. Involvement of CUL4 ubiquitin E3 ligases in regulating CDK inhibitors Dacapo/p27Kip1 and cyclin E degradation. Cell Cycle 2006, 5(1):71-77.
38. Houchins J.P., Yabe T., McSherry C., Bach F.H. DNA sequence analysis of NKG2, a family of related cDNA clones encoding type II integral membrane proteins on human natural killer cells. J. Exp. Med. 1991, 173(4):1017-1020.
39. Hrecka K., Gierszewska M., Srivastava S., Kozaczkiewicz L., Swanson S.K., Florens L., Washburn M.P., Skowronski J. Lentiviral Vpr usurps Cul4-DDB1[VprBP] E3 ubiquitin ligase to modulate cell cycle. Proc. Natl. Acad. Sci. USA 2007, 104(28):11778-11783.
40. Hrimech M., Yao X.J., Bachand F., Rougeau N., Cohen E.A. Human immunodeficiency virus type 1 (HIV-1) Vpr functions as an immediate-early protein during HIV-1 infection. J. Virol. 1999, 73(5):4101-4109.
41. Hu J., McCall C.M., Ohta T., Xiong Y. Targeted ubiquitination of CDT 1 by the DDB1-CUL4A-ROC1 ligase in response to DNA damage. Nat. Cell Biol. 2004, 6(10):1003-1009.
42. Huang J., Chen J. VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation. Oncogene 2008, 27(29):4056-4064.
43. Jacotot E., Ravagnan L., Loeffler M., Ferri K.F., Vieira H.L., Zamzami N., Costantini P., Druillennec S., Hoebeke J., Briand J.P., Irinopoulou T., Daugas E., Susin S.A., Cointe D., Xie Z.H., Reed J.C., Roques B.P., Kroemer G. The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore. J. Exp. Med. 2000, 191(1):33-46.
44. Jacquot G., Le Rouzic E., David A., Mazzolini J., Bouchet J., Bouaziz S., Niedergang F., Pancino G., Benichou S. Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. Retrovirology 2007, 4:84.
45. Jin J., Arias E.E., Chen J., Harper J.W., Walter J.C. A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. Mol. Cell 2006, 23(5):709-721.
46. Jonjic S., Polic B., Krmpotic A. Viral inhibitors of NKG2D ligands: friends or foes of immune surveillance?. Eur. J. Immunol. 2008, 38(11):2952-2956.
47. Jowett J.B., Planelles V., Poon B., Shah N.P., Chen M.L., Chen I.S. The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2 + M phase of the cell cycle. J. Virol. 1995, 69(10):6304-6313.
48. Kaushik R., Zhu X., Stranska R., Wu Y., Stevenson M. A cellular restriction dictates the permissivity of nondividing monocytes/macrophages to lentivirus and gammaretrovirus infection. Cell Host Microbe. 2009, 6(1):68-80.
49. Kedzierska K., Crowe S.M. The role of monocytes and macrophages in the pathogenesis of HIV-1 infection. Curr. Med. Chem. 2002, 9(21):1893-1903.
50. Kichler A., Pages J.C., Leborgne C., Druillennec S., Lenoir C., Coulaud D., Delain E., Le Cam E., Roques B.P., Danos O. Efficient DNA transfection mediated by the C-terminal domain of human immunodeficiency virus type 1 viral protein R. J. Virol. 2000, 74(12):5424-5431.
51. Kokoszka J.E., Waymire K.G., Levy S.E., Sligh J.E., Cai J., Jones D.P., MacGregor G.R., Wallace D.C. The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature 2004, 427(6973):461-465.
52. Kubin M., Cassiano L., Chalupny J., Chin W., Cosman D., Fanslow W., Mullberg J., Rousseau A.M., Ulrich D., Armitage R. ULBP1, 2, 3: novel MHC class I-related molecules that bind to human cytomegalovirus glycoprotein UL16, activate NK cells. Eur. J. Immunol. 2001, 31(5):1428-1437.
53. Le Rouzic E., Belaidouni N., Estrabaud E., Morel M., Rain J.C., Transy C., Margottin-Goguet F. HIV1 Vpr arrests the cell cycle by recruiting DCAF1/VprBP, a receptor of the Cul4-DDB1 ubiquitin ligase. Cell Cycle 2007, 6(2):182-188.
54. Le Rouzic E., Benichou S. The Vpr protein from HIV-1: distinct roles along the viral life cycle. Retrovirology 2005, 2(1):11.
55. Mahalingam S., Ayyavoo V., Patel M., Kieber-Emmons T., Weiner D.B. Nuclear import, virion incorporation, and cell cycle arrest/differentiation are mediated by distinct functional domains of human immunodeficiency virus type 1 Vpr. J. Virol. 1997, 71(9):6339-6347.
56. McGowan C.H., Russell P. The DNA damage response: sensing and signaling. Curr. Opin. Cell Biol. 2004, 16(6):629-633.
57. Morellet N., Bouaziz S., Petitjean P., Roques B.P. NMR structure of the HIV-1 regulatory protein VPR. J. Mol. Biol. 2003, 327(1):215-227.
58. Muthumani K., Hwang D.S., Desai B.M., Zhang D., Dayes N., Green D.R., Weiner D.B. HIV-1 Vpr induces apoptosis through caspase 9 in T cells and peripheral blood mononuclear cells. J. Biol. Chem. 2002, 277(40):37820-37831.
59. Nakagawa T., Shimizu S., Watanabe T., Yamaguchi O., Otsu K., Yamagata H., Inohara H., Kubo T., Tsujimoto Y. Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature 2005, 434(7033):652-658.
60. Ogawa K., Shibata R., Kiyomasu T., Higuchi I., Kishida Y., Ishimoto A., Adachi A. Mutational analysis of the human immunodeficiency virus vpr open reading frame. J. Virol. 1989, 63(9):4110-4114.
61. Orenstein J.M., Fox C., Wahl S.M. Macrophages as a source of HIV during opportunistic infections. Science 1997, 276(5320):1857-1861.
62. Pancio H.A., Vander Heyden N., Ratner L. The C-terminal proline-rich tail of human immunodeficiency virus type 2 Vpx is necessary for nuclear localization of the viral preintegration complex in nondividing cells. J. Virol. 2000, 74(13):6162-6167.
63. Pende D., Rivera P., Marcenaro S., Chang C.C., Biassoni R., Conte R., Kubin M., Cosman D., Ferrone S., Moretta L., Moretta A. Major histocompatibility complex class I-related chain A and UL16-binding protein expression on tumor cell lines of different histotypes: analysis of tumor susceptibility to NKG2D-dependent natural killer cell cytotoxicity. Cancer Res. 2002, 62(21):6178-6186.
64. Planelles V., Benichou S. Vpr and its interactions with cellular proteins. Curr. Top. Microbiol. Immunol. 2010, 339:177-200.
65. Planelles V., Jowett J.B., Li Q.X., Xie Y., Hahn B., Chen I.S. Vpr-induced cell cycle arrest is conserved among primate lentiviruses. J. Virol. 1996, 70(4):2516-2524.
66. Poon B., Jowett J.B., Stewart S.A., Armstrong R.W., Rishton G.M., Chen I.S. Human immunodeficiency virus type 1 vpr gene induces phenotypic effects similar to those of the DNA alkylating agent, nitrogen mustard. J. Virol. 1997, 71(5):3961-3971.
67. Re F., Braaten D., Franke E.K., Luban J. Human immunodeficiency virus type 1 Vpr arrests the cell cycle in G2 by inhibiting the activation of p34cdc2-cyclin B. J. Virol. 1995, 69(11):6859-6864.
68. Richard, J., Sindhu, S., Pham, T.N., Belzile, J.P., Cohen, E.A., 2009. HIV-1 Vpr upregulates expression of ligands for the activating NKG2D receptor and promotes NK cell-mediated killing. Blood.
69. Rogel M.E., Wu L.I., Emerman M. The human immunodeficiency virus type 1 vpr gene prevents cell proliferation during chronic infection. J. Virol. 1995, 69(2):882-888.
70. Roshal M., Kim B., Zhu Y., Nghiem P., Planelles V. Activation of the ATR-mediated DNA damage response by the HIV-1 viral protein R. J. Biol. Chem. 2003, 278(28):25879-25886.
71. Schrofelbauer B., Hakata Y., Landau N.R. HIV-1 Vpr function is mediated by interaction with the damage-specific DNA-binding protein DDB1. Proc. Natl. Acad. Sci. USA 2007, 104(10):4130-4135.
72. Schuler W., Wecker K., de Rocquigny H., Baudat Y., Sire J., Roques B.P. NMR structure of the (52-96) C-terminal domain of the HIV-1 regulatory protein Vpr: molecular insights into its biological functions. J. Mol. Biol. 1999, 285(5):2105-2117.
73. Schwartz S., Felber B.K., Pavlakis G.N. Expression of human immunodeficiency virus type 1 vif and vpr mRNAs is Rev-dependent and regulated by splicing. Virology 1991, 183(2):677-686.
74. Sharova N., Wu Y., Zhu X., Stranska R., Kaushik R., Sharkey M., Stevenson M. Primate lentiviral Vpx commandeers DDB1 to counteract a macrophage restriction. PLoS Pathog. 2008, 4(5):e1000057.
75. Sharp P.M., Bailes E., Stevenson M., Emerman M., Hahn B.H. Gene acquisition in HIV and SIV. Nature 1996, 383(6601):586-587.
76. Sherman M.P., Schubert U., Williams S.A., de Noronha C.M., Kreisberg J.F., Henklein P., Greene W.C. HIV-1 Vpr displays natural protein-transducing properties: implications for viral pathogenesis. Virology 2002, 302(1):95-105.
77. Shostak L.D., Ludlow J., Fisk J., Pursell S., Rimel B.J., Nguyen D., Rosenblatt J.D., Planelles V. Roles of p53 and caspases in the induction of cell cycle arrest and apoptosis by HIV-1 vpr. Exp. Cell Res. 1999, 251(1):156-165.
78. Srivastava S., Swanson S.K., Manel N., Florens L., Washburn M.P., Skowronski J. Lentiviral Vpx accessory factor targets VprBP/DCAF1 substrate adaptor for cullin 4 E3 ubiquitin ligase to enable macrophage infection. PLoS Pathog. 2008, 4(5):e1000059.
79. Stewart S.A., Poon B., Song J.Y., Chen I.S. Human immunodeficiency virus type 1 vpr induces apoptosis through caspase activation. J. Virol. 2000, 74(7):3105-3111.
80. Sugasawa K., Okuda Y., Saijo M., Nishi R., Matsuda N., Chu G., Mori T., Iwai S., Tanaka K., Tanaka K., Hanaoka F. UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex. Cell 2005, 121(3):387-400.
81. Tan L., Ehrlich E., Yu X.F. DDB1 and Cul4A are required for human immunodeficiency virus type 1 Vpr-induced G2 arrest. J. Virol. 2007, 81(19):10822-10830.
82. Tristem M., Marshall C., Karpas A., Hill F. Evolution of the primate lentiviruses: evidence from vpx and vpr. EMBO J. 1992, 11(9):3405-3412.
83. Tsujimoto Y., Shimizu S. Role of the mitochondrial membrane permeability transition in cell death. Apoptosis 2007, 12(5):835-840.
84. Tungaturthi P.K., Sawaya B.E., Singh S.P., Tomkowicz B., Ayyavoo V., Khalili K., Collman R.G., Amini S., Srinivasan A. Role of HIV-1 Vpr in AIDS pathogenesis: relevance and implications of intravirion, intracellular and free Vpr. Biomed. Pharmacother. 2003, 57(1):20-24.
85. Vieira H.L., Haouzi D., El Hamel C., Jacotot E., Belzacq A.S., Brenner C., Kroemer G. Permeabilization of the mitochondrial inner membrane during apoptosis: impact of the adenine nucleotide translocator. Cell Death Differ. 2000, 7(12):1146-1154.
86. Wang H., Zhai L., Xu J., Joo H.Y., Jackson S., Erdjument-Bromage H., Tempst P., Xiong Y., Zhang Y. Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage. Mol. Cell 2006, 22(3):383-394.
87. Wang L., Mukherjee S., Narayan O., Zhao L.J. Characterization of a leucine-zipper-like domain in Vpr protein of human immunodeficiency virus type 1. Gene 1996, 178(1-2):7-13.
88. Ward J., Bonaparte M., Sacks J., Guterman J., Fogli M., Mavilio D., Barker E. HIV modulates the expression of ligands important in triggering natural killer cell cytotoxic responses on infected primary T-cell blasts. Blood 2007, 110(4):1207-1214.
89. Ward J., Davis Z., DeHart J., Zimmerman E., Bosque A., Brunetta E., Mavilio D., Planelles V., Barker E. HIV-1 Vpr triggers natural killer cell-mediated lysis of infected cells through activation of the ATR-mediated DNA damage response. PLoS Pathog. 2009, 5(10):e1000613.
90. Wen X., Duus K.M., Friedrich T.D., de Noronha C.M. 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. 2007, 282(37):27046-27057.
91. Wong-Staal F., Chanda P.K., Ghrayeb J. Human immunodeficiency virus: the eighth gene. AIDS Res. Hum. Retroviruses 1987, 3(1):33-39.
92. Wu J., Song Y., Bakker A.B., Bauer S., Spies T., Lanier L.L., Phillips J.H. An activating immunoreceptor complex formed by NKG2D and DAP10. Science 1999, 285(5428):730-732.
93. Yu X.F., Yu Q.C., Essex M., Lee T.H. The vpx gene of simian immunodeficiency virus facilitates efficient viral replication in fresh lymphocytes and macrophage. J. Virol. 1991, 65(9):5088-5091.
94. Yuan H., Xie Y.M., Chen I.S. Depletion of Wee-1 kinase is necessary for both human immunodeficiency virus type 1 Vpr- and gamma irradiation-induced apoptosis. J. Virol. 2003, 77(3):2063-2070.
95. Zhao L.J., Mukherjee S., Narayan O. Biochemical mechanism of HIV-I Vpr function. Specific interaction with a cellular protein. J. Biol. Chem. 1994, 269(22):15577-15582.
96. Zhu Y., Gelbard H.A., Roshal M., Pursell S., Jamieson B.D., Planelles V. 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. 2001, 75(8):3791-3801.
97. Zimmerman E.S., Sherman M.P., Blackett J.L., Neidleman J.A., Kreis C., Mundt P., Williams S.A., Warmerdam M., Kahn J., Hecht F.M., Grant R.M., de Noronha C.M., Weyrich A.S., Greene W.C., Planelles V. Human immunodeficiency virus type 1 Vpr induces DNA replication stress in vitro and in vivo. J. Virol. 2006, 80(21):10407-10418.