HIV-1 viral genes and mitochondrial apoptosis

Apoptosis

Volumn 13, Issue 9, 2008, Pages 1088-1099

  Shedlock, Devon J ^a   Hwang, Daniel ^a   Choo, Andy Y ^b   Chung, Christopher W ^a   Muthumani, Karuppiah ^a   Weiner, David B ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Apoptosis; HIV 1; Mitochondria; Viral proteins

Indexed keywords

NEF PROTEIN; PROTEINASE; TRANSACTIVATOR PROTEIN; VIRUS ENVELOPE PROTEIN; VPR PROTEIN;

APOPTOSIS; CD4+ T LYMPHOCYTE; HOMEOSTASIS; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MITOCHONDRIAL MEMBRANE; MITOCHONDRION; MUTATION; PATHOGENESIS; POINT MUTATION; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; VIRUS GENE;

APOPTOSIS; GENES, VIRAL; HIV INFECTIONS; HIV-1; HUMANS; MITOCHONDRIA;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 49349095960     PISSN: 13608185     EISSN: 1573675X     Source Type: Journal    
DOI: 10.1007/s10495-008-0239-0     Document Type: Review

References (155)

1. Duve C (1975) Exploring cells with a centrifuge. Science 189:186-194 (New York, NY)
2. IE Scheffler 2001 A century of mitochondrial research: achievements and perspectives Mitochondrion 1 3 31 10.1016/S1567-7249(00)00002-7
3. MA Chattergoon K Muthumani Y Tamura 2008 DR5 activation of caspase-8 induces DC maturation and immune enhancement in vivo Mol Ther 16 419 426 10.1038/sj.mt.6300373
4. G Kroemer JC Reed 2000 Mitochondrial control of cell death Nat Med 6 513 519 10.1038/74994
5. Saraste M (1999) Oxidative phosphorylation at the fin de siecle. Science 283:1488-1493 (New York, NY)
6. HL Vieira D Haouzi C El Hamel 2000 Permeabilization of the mitochondrial inner membrane during apoptosis: impact of the adenine nucleotide translocator Cell Death Differ 7 1146 1154 10.1038/sj.cdd.4400778
7. Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281:1309-1312 (New York, NY)
8. G Kroemer B Dallaporta M Resche-Rigon 1998 The mitochondrial death/life regulator in apoptosis and necrosis Annu Rev Physiol 60 619 642 10.1146/annurev.physiol.60.1.619
9. E Jacotot P Costantini E Laboureau N Zamzami SA Susin G Kroemer 1999 Mitochondrial membrane permeabilization during the apoptotic process Ann NY Acad Sci 887 18 30
10. I Marzo C Brenner N Zamzami 1998 The permeability transition pore complex: a target for apoptosis regulation by caspases and bcl-2-related proteins J Exp Med 187 1261 1271 10.1084/jem.187.8.1261
11. DW Nicholson NA Thornberry 1997 Caspases: killer proteases Trends Biochem Sci 22 299 306 10.1016/S0968-0004(97)01085-2
12. G Kroemer 1997 The proto-oncogene Bcl-2 and its role in regulating apoptosis Nat Med 3 614 620 10.1038/nm0697-614
13. N Zamzami C Brenner I Marzo SA Susin G Kroemer 1998 Subcellular and submitochondrial mode of action of Bcl-2-like oncoproteins Oncogene 16 2265 2282 10.1038/sj.onc.1201989
14. DR Green 2000 Apoptotic pathways: paper wraps stone blunts scissors Cell 102 1 4 10.1016/S0092-8674(00)00003-9
15. MP Boldin TM Goncharov YV Goltsev D Wallach 1996 Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death Cell 85 803 815 10.1016/S0092-8674(00)81265-9
16. H Li H Zhu CJ Xu J Yuan 1998 Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis Cell 94 491 501 10.1016/S0092-8674(00)81590-1
17. X Luo I Budihardjo H Zou C Slaughter X Wang 1998 Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors Cell 94 481 490 10.1016/S0092- 8674(00)81589-5
18. Wei MC, Zong WX, Cheng EH et al (2001) Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292:727-730 (New York, NY)
19. F Li G Ambrosini EY Chu 1998 Control of apoptosis and mitotic spindle checkpoint by survivin Nature 396 580 584 10.1038/25141
20. F Quignon F De Bels M Koken J Feunteun JC Ameisen H de The 1998 PML induces a novel caspase-independent death process Nat Genet 20 259 265 10.1038/3068
21. J Xiang DT Chao SJ Korsmeyer 1996 BAX-induced cell death may not require interleukin 1 beta-converting enzyme-like proteases Proc Natl Acad Sci USA 93 14559 14563 10.1073/pnas.93.25.14559
22. Marzo I, Brenner C, Zamzami N et al (1998) Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis. Science 281:2027-2031 (New York, NY)
23. MG Vander Heiden NS Chandel EK Williamson PT Schumacker CB Thompson 1997 Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria Cell 91 627 637 10.1016/S0092-8674(00)80450-X
24. S Krajewski M Krajewska A Shabaik T Miyashita HG Wang JC Reed 1994 Immunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2 Am J Pathol 145 1323 1336
25. C Brenner H Cadiou HL Vieira 2000 Bcl-2 and Bax regulate the channel activity of the mitochondrial adenine nucleotide translocator Oncogene 19 329 336 10.1038/sj.onc.1203298
26. MM Nass S Nass 1963 Intramitochondrial Fibers with DNA Characteristics. I. Fixation and Electron Staining Reactions J Cell Biol 19 593 611 10.1083/jcb.19.3.593
27. GS Shadel DA Clayton 1997 Mitochondrial DNA maintenance in vertebrates Annu Rev Biochem 66 409 435 10.1146/annurev.biochem.66.1.409
28. DL Croteau VA Bohr 1997 Repair of oxidative damage to nuclear and mitochondrial DNA in mammalian cells J Biol Chem 272 25409 25412 10.1074/jbc.272.41.25409
29. DE Sawyer B Van Houten 1999 Repair of DNA damage in mitochondria Mutat Res 434 161 176
30. Attardi G (1993) The human mitochondrial genetic system. In: DiMauro S, Wallace DC (eds) Mitochondrial DNA in human pathology. Raven Press, New York, pp 9-25
31. P Giege A Brennicke 1999 RNA editing in Arabidopsis mitochondria effects 441 C to U changes in ORFs Proc Natl Acad Sci USA 96 15324 15329 10.1073/pnas.96.26.15324
32. Y Zhang LL Spremulli 1998 Roles of residues in mammalian mitochondrial elongation factor Ts in the interaction with mitochondrial and bacterial elongation factor Tu J Biol Chem 273 28142 28148 10.1074/jbc.273.43.28142
33. MF Bauer S Hofmann W Neupert M Brunner 2000 Protein translocation into mitochondria: the role of TIM complexes Trends Cell Biol 10 25 31 10.1016/S0962-8924(99)01684-0
34. G Schatz 1998 Protein transport. The doors to organelles Nature 395 439 440 10.1038/26620
35. A Cossarizza 2008 Apoptosis and HIV infection: about molecules and genes Curr Pharm Des 14 237 244 10.2174/138161208783413293
36. AG Dalgleish PC Beverley PR Clapham DH Crawford MF Greaves RA Weiss 1984 The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus Nature 312 763 767 10.1038/312763a0
37. JD Lifson MB Feinberg GR Reyes 1986 Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein Nature 323 725 728 10.1038/323725a0
38. Lifson JD, Reyes GR, McGrath MS, Stein BS, Engleman EG (1986) AIDS retrovirus induced cytopathology: giant cell formation and involvement of CD4 antigen. Science 232:1123-1127 (New York, NY)
39. H Choe M Farzan Y Sun 1996 The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates Cell 85 1135 1148 10.1016/S0092-8674(00)81313-6
40. H Deng R Liu W Ellmeier 1996 Identification of a major co-receptor for primary isolates of HIV-1 Nature 381 661 666 10.1038/381661a0
41. T Dragic V Litwin GP Allaway 1996 HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5 Nature 381 667 673 10.1038/381667a0
42. A Seth J Markee A Hoering 2001 Alterations in T cell phenotype and human immunodeficiency virus type 1-specific cytotoxicity after potent antiretroviral therapy J Infect Dis 183 722 729 10.1086/318816
43. DC Douek JM Brenchley MR Betts 2002 HIV preferentially infects HIV-specific CD4+ T cells Nature 417 95 98 10.1038/417095a
44. DD Ho AU Neumann AS Perelson W Chen JM Leonard M Markowitz 1995 Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection Nature 373 123 126 10.1038/373123a0
45. X Wei SK Ghosh ME Taylor 1995 Viral dynamics in human immunodeficiency virus type 1 infection Nature 373 117 122 10.1038/373117a0
46. PK Chattopadhyay DC Douek SJ Gange KR Chadwick M Hellerstein JB Margolick 2006 Longitudinal assessment of de novo T cell production in relation to HIV-associated T cell homeostasis failure AIDS Res Hum Retrov 22 501 507 10.1089/aid.2006.22.501
47. L Teixeira H Valdez JM McCune 2001 Poor CD4 T cell restoration after suppression of HIV-1 replication may reflect lower thymic function AIDS 15 1749 1756 10.1097/00002030-200109280-00002
48. NK Banda J Bernier DK Kurahara 1992 Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis J Exp Med 176 1099 1106 10.1084/jem.176.4.1099
49. H Groux G Torpier D Monte Y Mouton A Capron JC Ameisen 1992 Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals J Exp Med 175 331 340 10.1084/jem.175.2.331
50. Meyaard L, Otto SA, Jonker RR, Mijnster MJ, Keet RP, Miedema F (1992) Programmed death of T cells in HIV-1 infection. Science 257:217-219 (New York, NY)
51. K Sakai J Dimas MJ Lenardo 2006 The Vif and Vpr accessory proteins independently cause HIV-1-induced T cell cytopathicity and cell cycle arrest Proc Natl Acad Sci USA 103 3369 3374 10.1073/pnas.0509417103
52. DL Bolton BI Hahn EA Park LL Lehnhoff F Hornung MJ Lenardo 2002 Death of CD4(+) T-cell lines caused by human immunodeficiency virus type 1 does not depend on caspases or apoptosis J Virol 76 5094 5107 10.1128/JVI.76.10.5094- 5107.2002
53. MJ Lenardo SB Angleman V Bounkeua 2002 Cytopathic killing of peripheral blood CD4(+) T lymphocytes by human immunodeficiency virus type 1 appears necrotic rather than apoptotic and does not require env J Virol 76 5082 5093 10.1128/JVI.76.10.5082-5093.2002
54. C Speirs E van Nimwegen D Bolton 2005 Analysis of human immunodeficiency virus cytopathicity by using a new method for quantitating viral dynamics in cell culture J Virol 79 4025 4032 10.1128/JVI.79.7.4025-4032.2005
55. Ott M, Emiliani S, Van Lint C et al (1997) Immune hyperactivation of HIV-1-infected T cells mediated by Tat and the CD28 pathway. Science 275:1481-1485 (New York, NY)
56. A Cossarizza C Ortolani C Mussini 1995 Massive activation of immune cells with an intact T cell repertoire in acute human immunodeficiency virus syndrome J Infect Dis 172 105 112
57. PJ Norris BL Pappalardo B Custer G Spotts FM Hecht MP Busch 2006 Elevations in IL-10, TNF-alpha, and IFN-gamma from the earliest point of HIV Type 1 infection AIDS Res Hum Retrov 22 757 762 10.1089/aid.2006.22.757
58. BR Cullen 1998 HIV-1 auxiliary proteins: making connections in a dying cell Cell 93 685 692 10.1016/S0092-8674(00)81431-2
59. ML Gougeon L Montagnier 1999 Programmed cell death as a mechanism of CD4 and CD8 T cell deletion in AIDS. Molecular control and effect of highly active anti-retroviral therapy Ann NY Acad Sci 887 199 212
60. H Naora ML Gougeon 1999 Interleukin-15 is a potent survival factor in the prevention of spontaneous but not CD95-induced apoptosis in CD4 and CD8 T lymphocytes of HIV-infected individuals. Correlation with its ability to increase BCL-2 expression Cell Death Differ 6 1002 1011 10.1038/sj.cdd.4400575
61. M Castedo A Macho N Zamzami 1995 Mitochondrial perturbations define lymphocytes undergoing apoptotic depletion in vivo Eur J Immunol 25 3277 3284 10.1002/eji.1830251212
62. A Cossarizza C Mussini N Mongiardo 1997 Mitochondria alterations and dramatic tendency to undergo apoptosis in peripheral blood lymphocytes during acute HIV syndrome AIDS 11 19 26 10.1097/00002030-199701000-00004
63. KF Ferri E Jacotot J Blanco 2000 Apoptosis control in syncytia induced by the HIV type 1-envelope glycoprotein complex: role of mitochondria and caspases J Exp Med 192 1081 1092 10.1084/jem.192.8.1081
64. DC Chan D Fass JM Berger PS Kim 1997 Core structure of gp41 from the HIV envelope glycoprotein Cell 89 263 273 10.1016/S0092-8674(00)80205-6
65. JF Zagury H Cantalloube A Achour 1993 Striking similarities between HIV-1 Env protein and the apoptosis mediating cell surface antigen Fas. Role in the pathogenesis of AIDS Biomed Pharmacother 47 331 335
66. T Orlikowsky ZQ Wang A Dudhane H Horowitz G Riethmuller MK Hoffmann 1997 Cytotoxic monocytes in the blood of HIV type 1-infected subjects destroy targeted T cells in a CD95-dependent fashion AIDS Res Hum Retrov 13 953 960
67. PD Katsikis ME Garcia-Ojeda ES Wunderlich 1996 Activation-induced peripheral blood T cell apoptosis is Fas independent in HIV-infected individuals Int Immunol 8 1311 1317 10.1093/intimm/8.8.1311
68. ZQ Wang A Dudhane T Orlikowsky 1994 CD4 engagement induces Fas antigen-dependent apoptosis of T cells in vivo Eur J Immunol 24 1549 1552 10.1002/eji.1830240714
69. F Hashimoto N Oyaizu VS Kalyanaraman S Pahwa 1997 Modulation of Bcl-2 protein by CD4 cross-linking: a possible mechanism for lymphocyte apoptosis in human immunodeficiency virus infection and for rescue of apoptosis by interleukin-2 Blood 90 745 753
70. PH Krammer 2000 CD95's deadly mission in the immune system Nature 407 789 795 10.1038/35037728
71. C Twu NQ Liu W Popik 2002 Cardiomyocytes undergo apoptosis in human immunodeficiency virus cardiomyopathy through mitochondrion- and death receptor-controlled pathways Proc Natl Acad Sci USA 99 14386 14391 10.1073/pnas.212327899
72. XN Xu B Laffert GR Screaton 1999 Induction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain J Exp Med 189 1489 1496 10.1084/jem.189.9.1489
73. G Zauli D Gibellini P Secchiero 1999 Human immunodeficiency virus type 1 Nef protein sensitizes CD4(+) T lymphoid cells to apoptosis via functional upregulation of the CD95/CD95 ligand pathway Blood 93 1000 1010
74. G Herbein U Mahlknecht F Batliwalla 1998 Apoptosis of CD8+ T cells is mediated by macrophages through interaction of HIV gp120 with chemokine receptor CXCR4 Nature 395 189 194 10.1038/26026
75. D Cefai M Ferrer N Serpente 1992 Internalization of HIV glycoprotein gp120 is associated with down-modulation of membrane CD4 and p56lck together with impairment of T cell activation J Immunol 149 285 294
76. M Kaul SA Lipton 1999 Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis Proc Natl Acad Sci USA 96 8212 8216 10.1073/pnas.96.14.8212
77. H Ohnimus M Heinkelein C Jassoy 1997 Apoptotic cell death upon contact of CD4+ T lymphocytes with HIV glycoprotein-expressing cells is mediated by caspases but bypasses CD95 (Fas/Apo-1) and TNF receptor 1 J Immunol 159 5246 5252
78. C Berndt B Mopps S Angermuller P Gierschik PH Krammer 1998 CXCR4 and CD4 mediate a rapid CD95-independent cell death in CD4(+) T cells Proc Natl Acad Sci USA 95 12556 12561 10.1073/pnas.95.21.12556
79. CD Fermin RF Garry 1992 Membrane alterations linked to early interactions of HIV with the cell surface Virology 191 941 946 10.1016/0042-6822(92)90269-U
80. A Yusim L Franklin S Brooke O Ajilore R Sapolsky 2000 Glucocorticoids exacerbate the deleterious effects of gp120 in hippocampal and cortical explants J Neurochem 74 1000 1007 10.1046/j.1471-4159.2000.0741000.x
81. J Sodroski WC Goh C Rosen K Campbell WA Haseltine 1986 Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity Nature 322 470 474 10.1038/322470a0
82. S Wang J York W Shu MO Stoller JH Nunberg M Lu 2002 Interhelical interactions in the gp41 core: implications for activation of HIV-1 membrane fusion Biochemistry 41 7283 7292 10.1021/bi025648y
83. H Garg R Blumenthal 2006 HIV gp41-induced apoptosis is mediated by caspase-3-dependent mitochondrial depolarization, which is inhibited by HIV protease inhibitor nelfinavir J Leukoc Biol 79 351 362 10.1189/jlb.0805430
84. M Castedo T Roumier J Blanco 2002 Sequential involvement of Cdk1, mTOR and p53 in apoptosis induced by the HIV-1 envelope EMBO J 21 4070 4080 10.1093/emboj/cdf391
85. A Sylwester S Murphy D Shutt DR Soll 1997 HIV-induced T cell syncytia are self-perpetuating and the primary cause of T cell death in culture J Immunol 158 3996 4007
86. E Bossy-Wetzel DR Green 1999 Caspases induce cytochrome c release from mitochondria by activating cytosolic factors J Biol Chem 274 17484 17490 10.1074/jbc.274.25.17484
87. A Rasola D Gramaglia C Boccaccio PM Comoglio 2001 Apoptosis enhancement by the HIV-1 Nef protein J Immunol 166 81 88
88. CO James MB Huang M Khan M Garcia-Barrio MD Powell VC Bond 2004 Extracellular Nef protein targets CD4+ T cells for apoptosis by interacting with CXCR4 surface receptors J Virol 78 3099 3109 10.1128/JVI.78.6.3099-3109.2004
89. KL Collins BK Chen SA Kalams BD Walker D Baltimore 1998 HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes Nature 391 397 401 10.1038/34929
90. M Inoue Y Koga D Djordjijevic 1993 Down-regulation of CD4 molecules by the expression of Nef: a quantitative analysis of CD4 antigens on the cell surfaces Int Immunol 5 1067 1073 10.1093/intimm/5.9.1067
91. OW Lindwasser R Chaudhuri JS Bonifacino 2007 Mechanisms of CD4 downregulation by the Nef and Vpu proteins of primate immunodeficiency viruses Curr Mol Med 7 171 184 10.2174/156652407780059177
92. R Geleziunas W Xu K Takeda H Ichijo WC Greene 2001 HIV-1 Nef inhibits ASK1-dependent death signalling providing a potential mechanism for protecting the infected host cell Nature 410 834 838 10.1038/35071111
93. D Wolf V Witte B Laffert 2001 HIV-1 Nef associated PAK and PI3-kinases stimulate Akt-independent Bad-phosphorylation to induce anti-apoptotic signals Nat Med 7 1217 1224 10.1038/nm1101-1217
94. M Li-Weber O Laur K Dern PH Krammer 2000 T cell activation-induced and HIV tat-enhanced CD95(APO-1/Fas) ligand transcription involves NF-kappaB Eur J Immunol 30 661 670 10.1002/1521-4141(200002)30:2≤661::AID-IMMU661≥3.0. CO;2-L
95. B Ensoli G Barillari SZ Salahuddin RC Gallo F Wong-Staal 1990 Tat protein of HIV-1 stimulates growth of cells derived from Kaposi's sarcoma lesions of AIDS patients Nature 345 84 86 10.1038/345084a0
96. TW McCloskey M Ott E Tribble 1997 Dual role of HIV Tat in regulation of apoptosis in T cells J Immunol 158 1014 1019
97. MO Westendorp R Frank C Ochsenbauer 1995 Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120 Nature 375 497 500 10.1038/375497a0
98. KJ Sastry MC Marin PN Nehete K McConnell AK el-Naggar TJ McDonnell 1996 Expression of human immunodeficiency virus type I tat results in down-regulation of bcl-2 and induction of apoptosis in hematopoietic cells Oncogene 13 487 493
99. SR Bartz M Emerman 1999 Human immunodeficiency virus type 1 Tat induces apoptosis and increases sensitivity to apoptotic signals by up-regulating FLICE/caspase-8 J Virol 73 1956 1963
100. D Gibellini MC Re C Ponti 2005 HIV-1 Tat protein concomitantly down-regulates apical caspase-10 and up-regulates c-FLIP in lymphoid T cells: a potential molecular mechanism to escape TRAIL cytotoxicity J Cell Physiol 203 547 556 10.1002/jcp. 20252
101. Li CJ, Friedman DJ, Wang C, Metelev V, Pardee AB (1995) Induction of apoptosis in uninfected lymphocytes by HIV-1 Tat protein. Science 268:429-431 (New York, NY)
102. MO Westendorp VA Shatrov K Schulze-Osthoff 1995 HIV-1 Tat potentiates TNF-induced NF-kappa B activation and cytotoxicity by altering the cellular redox state EMBO J 14 546 554
103. M Creaven F Hans V Mutskov 1999 Control of the histone-acetyltransferase activity of Tip60 by the HIV-1 transactivator protein, Tat Biochemistry 38 8826 8830 10.1021/bi9907274
104. II Kruman A Nath MP Mattson 1998 HIV-1 protein Tat induces apoptosis of hippocampal neurons by a mechanism involving caspase activation, calcium overload, and oxidative stress Exp Neurol 154 276 288 10.1006/exnr.1998.6958
105. D Chen M Wang S Zhou Q Zhou 2002 HIV-1 Tat targets microtubules to induce apoptosis, a process promoted by the pro-apoptotic Bcl-2 relative Bim EMBO J 21 6801 6810 10.1093/emboj/cdf683
106. PR Strack MW Frey CJ Rizzo 1996 Apoptosis mediated by HIV protease is preceded by cleavage of Bcl-2 Proc Natl Acad Sci USA 93 9571 9576 10.1073/pnas.93.18.9571
107. Z Nie BN Phenix JJ Lum 2002 HIV-1 protease processes procaspase 8 to cause mitochondrial release of cytochrome c, caspase cleavage and nuclear fragmentation Cell Death Differ 9 1172 1184 10.1038/sj.cdd.4401094
108. Z Nie GD Bren SR Vlahakis 2007 Human immunodeficiency virus type 1 protease cleaves procaspase 8 in vivo J Virol 81 6947 6956 10.1128/JVI.02798-06
109. JS Gibbs AA Lackner SM Lang 1995 Progression to AIDS in the absence of a gene for vpr or vpx J Virol 69 2378 2383
110. EA Cohen G Dehni JG Sodroski WA Haseltine 1990 Human immunodeficiency virus vpr product is a virion-associated regulatory protein J Virol 64 3097 3099
111. SM Lang M Weeger C Stahl-Hennig 1993 Importance of vpr for infection of rhesus monkeys with simian immunodeficiency virus J Virol 67 902 912
112. DN Levy Y Refaeli DB Weiner 1995 Extracellular Vpr protein increases cellular permissiveness to human immunodeficiency virus replication and reactivates virus from latency J Virol 69 1243 1252
113. F Bachand XJ Yao M Hrimech N Rougeau EA Cohen 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 10.1074/jbc.274.13.9083
114. M Kamata Y Aida 2000 Two putative alpha-helical domains of human immunodeficiency virus type 1 Vpr mediate nuclear localization by at least two mechanisms J Virol 74 7179 7186 10.1128/JVI.74.15.7179-7186.2000
115. YL Lu P Spearman L Ratner 1993 Human immunodeficiency virus type 1 viral protein R localization in infected cells and virions J Virol 67 6542 6550
116. S Mahalingam RG Collman M Patel CE Monken A Srinivasan 1995 Functional analysis of HIV-1 Vpr: identification of determinants essential for subcellular localization Virology 212 331 339 10.1006/viro.1995.1490
117. RA Subbramanian A Kessous-Elbaz R Lodge 1998 Human immunodeficiency virus type 1 Vpr is a positive regulator of viral transcription and infectivity in primary human macrophages J Exp Med 187 1103 1111 10.1084/jem.187.7.1103
118. NK Heinzinger MI Bukinsky SA Haggerty 1994 The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells Proc Natl Acad Sci USA 91 7311 7315 10.1073/pnas.91.15.7311
119. P Gallay T Hope D Chin D Trono 1997 HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway Proc Natl Acad Sci USA 94 9825 9830 10.1073/pnas.94.18.9825
120. MI Bukrinsky N Sharova TL McDonald T Pushkarskaya WG Tarpley M Stevenson 1993 Association of integrase, matrix, and reverse transcriptase antigens of human immunodeficiency virus type 1 with viral nucleic acids following acute infection Proc Natl Acad Sci USA 90 6125 6129 10.1073/pnas.90.13.6125
121. V Zennou C Petit D Guetard U Nerhbass L Montagnier P Charneau 2000 HIV-1 genome nuclear import is mediated by a central DNA flap Cell 101 173 185 10.1016/S0092-8674(00)80828-4
122. S Popov M Rexach L Ratner G Blobel M Bukrinsky 1998 Viral protein R regulates docking of the HIV-1 preintegration complex to the nuclear pore complex J Biol Chem 273 13347 13352 10.1074/jbc.273.21.13347
123. RI Connor BK Chen S Choe NR Landau 1995 Vpr is required for efficient replication of human immunodeficiency virus type-1 in mononuclear phagocytes Virology 206 935 944 10.1006/viro.1995.1016
124. DA Eckstein MP Sherman ML Penn 2001 HIV-1 Vpr enhances viral burden by facilitating infection of tissue macrophages but not nondividing CD4 + T cells J Exp Med 194 1407 1419 10.1084/jem.194.10.1407
125. P Westervelt T Henkel DB Trowbridge 1992 Dual regulation of silent and productive infection in monocytes by distinct human immunodeficiency virus type 1 determinants J Virol 66 3925 3931
126. DN Levy Y Refaeli DB Weiner 1995 The vpr regulatory gene of HIV Curr Top Microbiol Immunol 193 209 236
127. S Mahalingam V Ayyavoo M Patel 1998 HIV-1 Vpr interacts with a human 34-kDa mov34 homologue, a cellular factor linked to the G2/M phase transition of the mammalian cell cycle Proc Natl Acad Sci USA 95 3419 3424 10.1073/pnas.95.7.3419
128. J He S Choe R Walker P Di Marzio DO Morgan NR Landau 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
129. JB Jowett V Planelles B Poon NP Shah ML Chen IS Chen 1995 The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2 + M phase of the cell cycle J Virol 69 6304 6313
130. WC Goh ME Rogel CM Kinsey 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 10.1038/nm0198-065
131. SA Stewart B Poon JB Jowett IS Chen 1997 Human immunodeficiency virus type 1 Vpr induces apoptosis following cell cycle arrest J Virol 71 5579 5592
132. SA Stewart B Poon JY Song IS Chen 2000 Human immunodeficiency virus type 1 vpr induces apoptosis through caspase activation J Virol 74 3105 3111 10.1128/JVI.74.7.3105-3111.2000
133. V Ayyavoo S Mahalingam Y Rafaeli 1997 HIV-1 viral protein R (Vpr) regulates viral replication and cellular proliferation in T cells and monocytoid cells in vitro J Leukoc Biol 62 93 99
134. K Muthumani AY Choo DS Hwang 2003 Mechanism of HIV-1 viral protein R-induced apoptosis Biochem Biophys Res Commun 304 583 592 10.1016/S0006- 291X(03)00631-4
135. K Muthumani DS Hwang BM Desai 2002 HIV-1 Vpr induces apoptosis through caspase 9 in T cells and peripheral blood mononuclear cells J Biol Chem 277 37820 37831 10.1074/jbc.M205313200
136. Poon B, Grovit-Ferbas K, Stewart SA, Chen IS (1998) Cell cycle arrest by Vpr in HIV-1 virions and insensitivity to antiretroviral agents. Science 281:266-269 (New York, NY)
137. CA Patel M Mukhtar RJ Pomerantz 2000 Human immunodeficiency virus type 1 Vpr induces apoptosis in human neuronal cells J Virol 74 9717 9726 10.1128/JVI.74.20.9717-9726.2000
138. SC Piller P Jans PW Gage DA Jans 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 USA 95 4595 4600 10.1073/pnas.95.8.4595
139. V Ayyavoo A Mahboubi S Mahalingam 1997 HIV-1 Vpr suppresses immune activation and apoptosis through regulation of nuclear factor kappa B Nat Med 3 1117 1123 10.1038/nm1097-1117
140. T Kino A Gragerov JB Kopp RH Stauber GN Pavlakis GP Chrousos 1999 The HIV-1 virion-associated protein vpr is a coactivator of the human glucocorticoid receptor J Exp Med 189 51 62 10.1084/jem.189.1.51
141. E Jacotot L Ravagnan M Loeffler 2000 The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore J Exp Med 191 33 46 10.1084/jem.191.1.33
142. E Jacotot KF Ferri C El Hamel 2001 Control of mitochondrial membrane permeabilization by adenine nucleotide translocator interacting with HIV-1 viral protein rR and Bcl-2 J Exp Med 193 509 519 10.1084/jem.193.4.509
143. T Roumier HL Vieira M Castedo 2002 The C-terminal moiety of HIV-1 Vpr induces cell death via a caspase-independent mitochondrial pathway Cell Death Differ 9 1212 1219 10.1038/sj.cdd.4401089
144. S Moretti S Marcellini A Boschini 2000 Apoptosis and apoptosis-associated perturbations of peripheral blood lymphocytes during HIV infection: comparison between AIDS patients and asymptomatic long-term non-progressors Clin Exp Immunol 122 364 373 10.1046/j.1365-2249.2000.01375.x
145. Y Cao L Qin L Zhang J Safrit DD Ho 1995 Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection N Engl J Med 332 201 208 10.1056/NEJM199501263320401
146. ML Gougeon H Lecoeur A Dulioust 1996 Programmed cell death in peripheral lymphocytes from HIV-infected persons: increased susceptibility to apoptosis of CD4 and CD8 T cells correlates with lymphocyte activation and with disease progression J Immunol 156 3509 3520
147. JJ Lum OJ Cohen Z Nie 2003 Vpr R77Q is associated with long-term nonprogressive HIV infection and impaired induction of apoptosis J Clin Invest 111 1547 1554
148. RM Gulick JW Mellors D Havlir 1997 Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy N Engl J Med 337 734 739 10.1056/NEJM199709113371102
149. SM Hammer KE Squires MD Hughes 1997 A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team N Engl J Med 337 725 733 10.1056/NEJM199709113371101
150. AD Badley K Parato DW Cameron 1999 Dynamic correlation of apoptosis and immune activation during treatment of HIV infection Cell Death Differ 6 420 432 10.1038/sj.cdd.4400509
151. DP Kotler T Shimada G Snow 1998 Effect of combination antiretroviral therapy upon rectal mucosal HIV RNA burden and mononuclear cell apoptosis AIDS 12 597 604 10.1097/00002030-199806000-00008
152. BN Phenix JJ Lum Z Nie J Sanchez-Dardon AD Badley 2001 Antiapoptotic mechanism of HIV protease inhibitors: preventing mitochondrial transmembrane potential loss Blood 98 1078 1085 10.1182/blood.V98.4.1078
153. FF Weichold JL Bryant S Pati O Barabitskaya RC Gallo MS Reitz Jr 1999 HIV-1 protease inhibitor ritonavir modulates susceptibility to apoptosis of uninfected T cells J Hum Virol 2 261 269
154. J Blanco J Barretina KF Ferri 2003 Cell-surface-expressed HIV-1 envelope induces the death of CD4 T cells during GP41-mediated hemifusion-like events Virology 305 318 329 10.1006/viro.2002.1764
155. D Vittecoq C Jardel C Barthelemy 2002 Mitochondrial damage associated with long-term antiretroviral treatment: associated alteration or causal disorder? J Acquired Immune Defic Syndr 31 299 308