103
Views
20
CrossRef citations to date
0
Altmetric
Original Article

Pathogenesis of HIV-1 Infection Within Bone Marrow Cells

, , , , &
Pages 497-515 | Received 10 Oct 1999, Published online: 01 Jul 2009

References

  • Spivak J L, Bender B S, Quinn T C. Hematological abnormalities in AIDS. Amer. J. Med. 1984; 77: 225–2128
  • Frontiera M, Myers A M. Peripheral blood and bone marrow abnormalities in AIDS. West. J. Med. 1987; 147: 157–160
  • Fauci A S. The human immunodeficiency virus: Infectivity and mechanisms of pathogenesis. Science 1988; 239: 617–622
  • Zon L I, Arkin C, Groopman J E. Hematological manifestations of the human immunodeficiency virus. Brit. J. Hematol. 1987; 66: 251–256
  • Scadden D T, Zon L I, Groopman J E. Pathophysiology and management of HIV‐associated hematological disorders. Blood 1989; 74: 1455–1463
  • Coyle T E. Hematologic complications of human immunodeficiency virus infection and the acquired immunodeficiency syndrome. Med. Clinics N. Amer. 1997; 81: 449–463
  • Ho D D, Pomerantz R J, Kaplan J C. Pathogenesis of infection with human immunodeficiency virus. N. Engl. J. Med. 1987; 317: 278–286
  • Chelucci C, Federico M, Guerriero R, Mattia G, Casella I, Pelosi E, Testa U, Mariani G, Hassan H J, Peschle C. Productive human immunodeficiency virus‐1 infection of purified megakaryocytic progenitors/precursors and maturing megakaryocytes. Blood 1998; 91: 1225–1234
  • Weichold F F, Zella D, Barabitskaja O, Maciejewski J P, Dunn D E, Sloand E M, Young N S. Neither human immunodeficiency virus‐1 (HIV‐1) nor HIV‐2 infect most‐primitive human hematopoietic stem cells as assessed in long‐term bone marrow cultures. Blood 1998; 91: 907–915
  • Sben H, Cheng T, Preffer F I, Dombkowski D, Tomasson M H, Goland D E, Yang O, Hofmann W, Sodroski J G, Luster A D, Scadden D T. Intrinsic human immunodeficiency virus type 1 resistance of hematopoietic stem cells despite co‐receptor expression. J. Virol. 1999; 73: 728–737
  • Potts B J, Hoggan M, Lamperthy L, Spivak J. Replication of HIV‐1 and HIV‐1 in human bone marrow cultures. Virology 1992; 188: 840–849
  • Chelucci C, Hassan J H, Locardi C, Bulgarini D, Pelois E, Mariano G, Testa U, Federico M, Valtieri M, Peschle C. In vitro human immunodeficiency virus‐1 infection of purified hematopoietic progenitors in single cell culture. Blood 1995; 85: 1181–1187
  • Lunardi‐Iskandar Y, Georgoulias V, Bertoli A M, Augery‐Bourget Y, Ammar A, Vittecoq D, Rosenbaum W, Meyer P, Jasmin C. Impaired in vitro proliferation of hematopoietic precursors in HIV‐1‐infected subjects. Leuk. Res. 1989; 13: 573
  • Cen D, Zauli G, Szarnicki R, David B R. Effect of different human immunodeficiency virus type 1 (HIV‐1) isolates on long‐term bone marrow haemopoiesis. Br. J. Hematol. 1993; 85: 596–402
  • Neal T F, Holland H K, Baum C M, Villinger F, Ansari A A, Sari R, Wingard J R, Fleming W H. CD34+ progenitor cells from asymptomatic patients are not a major reservoir for human immunodeficiency virus‐1. Blood 1995; 86: 1749–1756
  • DeLuca A, Teofili L, Antinori A, Iovino M S, Mencarini P, Visconti E, Tamburrini E, Leone G, Ortona L. Haematopoietic CD34+ progenitor cells are not infected by HIV‐1 in vivo but show impaired clonogenesis. Br. J. Haematol. 1993; 85: 20–24
  • Louache F, Henri A, Bettaieb A, Oksenhendler E, Raguin G, Tulliez M, Vainchenker W. Role of human immunodeficiency virus replication in defective in vitro growth of hematopoietic progenitors. Blood 1992; 80: 2991–2999
  • Re M C, Zauli G, Gibellini D, Furlini G, Ramazzotti E, Monari P, Ranieri S, Capitani S, LaPlaca M. Uninfected haematopoietic progenitor (CD34+) cells purified from the bone marrow of AIDS patients are committed to apoptotic cell death in culture. AIDS 1993; 7: 1049–1055
  • Stanley S K, Kessler S W, Justement J S, Schnittman S M, Greenhouse J J, Brown C C, Musongela L, Musey K, Kapita B, Fauci A S. CD34+ bone marrow cells are infected with HIV in a subset of seropositive individuals. J. Immunol. 1992; 149: 689–497
  • Davis B R, Schwartz D H, Marx J C, Johnson C E, Berry J M, Lyding J, Merigan T C, Zander A. Absent or rare human immunodeficiency virus infection of bone marrow stem/progenitor cells in vivo. J. Virol. 1991; 65: 1985–1990
  • Vainchenker W, Louache F. Loss of primitive hematopoietic progenitors in patients with human immunodeficiency virus infection. Blood 1996; 88: 4568
  • Moses A, Nelson J, Bagby G C, Jr. The influence of human immunodeficiency virus‐1 on hematopoiesis. Blood 1998; 91: 1479–1495
  • Vignoli M, Stecca B, Furlini G, Re M C, Mantovani V, Zauli G, Visani G, Colangeli V, LaPlaca M. Impaired telomerase activity in uninfected haematopoietic progenitors in HIV‐1‐infected patients. AIDS 1998; 12: 999–1005
  • Nielsen S D, Ersboll A K, Mathiesen L, Nielsen J O, Hansen J ‐E. HighIy active antiretroviral therapy normalizes the function of progenitor cells in human immunodeficiency virus‐infected patients. J. Infect. Dis. 1998; 178: 1299–1305
  • Finzi D, Blankson J, Silicano J D, Margolick J B, Chadwick K, Pierson T, Smith K, Lisziewica J, Lori F, Flexner C, Quinn T C, Chaisson R E, Rosenberg E, Walker B, Gange S, Gallant J, Silicano R F. Latent infection of CD4+ T cells provide a mechanism for lifelong persistence of HIV‐1, even in patients on effective combination therapy. Nature Med 1999; 5: 512–517
  • Pomerantz R J. Residual HIV‐1 disease in the era of highly active antiretroviral therapy. Editorial. N. Engl. J. Med. 1999, In Press
  • Zhang H, Dornadula G, Beumont M, Livornese L, Van Uitert B, Henning K, Pomerantz R J. Human immunodeficiency virus type 1 in the semen of men receiving highly active antiretroviral therapy. N. Engl. J. Med. 1998; 339: 1803–9
  • Gill V, Shattock J, Scopes J, Hayes P, Freedman A R, Griffin D E, Gordon‐Smith E C, Gibson F M. Human immunodeficiency virus infection impairs hematopoiesis in long‐term bone marrow cultures: Non‐reversal by nucleoside analogues. J. Infect. Dis. 1997; 176: 1510–6
  • Sloand E M, Young N S, Sato T, Kumar P, Kim S, Weichold F F, Maciejewski J P. Secondary colony formation after long‐term bone marrow culture using peripheral blood and bone marrow of HIV‐1‐infected patients. AIDS 1997; 11: 1547–1553
  • Lunardi‐Iskander Y, Georgoulias V, Bertli A M, Augery‐Bourgef Y, Ammar A, Vittecoqu D, Rosenbaum W, Meyer P, Jasmin C. Impaired in vitro proliferation of hematopoietic precursors in HIV‐1‐infected subjects. Leuk. Res. 1989; 13573
  • Zhao S ‐F, Li W, Domadula G, Dicker D, Hoxie J, Peiper S C, Pomerantz R J, Duan L ‐X. Chemokine receptors and the molecular basis for HIV‐1 entry into peripheral hematopoietic stem cells. J. Infect. Dis. 1998; 178: 1623–1634
  • Zauli G, Furlini G, Vitale M, Re M C, Gibellini D, Zamai L, Visano G, Borgatti P, Capitano S, LaPlaca M. A subset of human CD34+ hematopoietic progenitors express low levels of CD4, the high affinity receptor for human immunodeficiency virus type 1. Blood 1994; 84: 1896–1905
  • Koka P S, Fraser J K, Bryson Y, Bristol G C, Aldrovandi G M, Daar E S, Zack J A. Human immunodeficiency virus inhibits multi‐lineage hematopoiesis in vivo. J. Virol. 1998; 72: 5121–5127
  • Jenkins M, Hanley M B, Moreno M B, Wieder E, McCune J M. Human immunodeficiency virus‐1 infection interrupts thymopoiesis and multi‐lineage hematopoiesis in viva. Blood 1998; 91: 2672–2678
  • Schwartz G N, Kessler S W, Rothwell S W, Burrell L M, Reid T J, Meltzer M S, Wright D G. Inhibitory effects of HIV‐1‐infected stromal cell layers on the production of myeloid progenitor cells in human long‐term bone marrow culture. Exp. Hematol. 1995; 22: 1288
  • Moses A V, Williams S, Heneveld M L, Strussenberg J, Rarick M, Loveless M, Bagby G, Nelson J A. Human immunodeficiency virus infection of bone marrow endothelium reduces induction of stromal hematopoietic growth factors. Blood 1996; 87: 919–925
  • Mosca J D, Kaushal S, Gartner S, Kessler S W, LaRussa V F, Terwilliger E F, Kim J H, Carroll R G, Hall E R, Perrera Yu LP, Zhipeng Ritchey DW, Xu J, St. Louis D C, Mayers D L. Characterization of a human stromal cell line supporting hematopoietic progenitor cell proliferation: Effect of HIV expression. J. Biomed. Sci. 1995; 2: 330–342
  • Scadden D T, Zeira M, Woon A, Wang Z, Schieve L, Ikeuchi K, Lim B, Groopman J E. Human immunodeficiency virus infection of human bone marrow stromal fibroblasts. Blood 1990; 76: 317–322
  • Canque B, Maradin A, Rosenzwaig M, Louache F, Vainchenker W, Gluckman J C. Susceptibility of human bone marrow stromal cells to human immunodeficiency virus (HIV). Virology 1995; 208: 779–83
  • Sun N CJ, Shapshak P, Lachant N A, Hsu M ‐Y, Sieger L, Schmid P, Geall G, Imagawa D T. Bone marrow examination in patients with AIDS and AIDS‐related complex (ARC). Amer. J. Clin. Pathol. 1989; 92: 589–594
  • Weiser B, Burger H, Campbell P, Donelan S, Mladenovic J. HIV type 1 RNA expression in bone marrows of patients with a spectrum of disease. AIDS Res. and Human Retroviruses 1996; 12: 1551–1559
  • Kitano K, Abboud C N, Ryan D H, Quan S G, Baldwin G C, Golde D W. Macrophage‐active colony‐stimulating factors enhance human immunodeficiency virus type 1 infection in bone marrow stem cells. Blood 1991; 77: 1699–1705
  • Gill V, Shattock R J, Freedman A R, et al. Macrophages are the major target cell for HIV infection in long‐term bone marrow culture and demonstrate dual susceptibility to lymphocytotropic and monocytotropic strains of HIV‐1. Br. J. Hematol. 1996; 93: 30–7
  • Sugiura K, Oyaizu N, Pahway R, Kalyanaraman V S, Pahwa S. Effect of human immunodeficiency virus‐1 envelope glycoprotein on in vivo hematopoiesis of umbilical cord blood. Blood 1992; 80: 1463–1469
  • Rameshwar P, Denny T N, Gascon P. Enhanced HIV‐1 activity in bone marrow can lead to myelopoietic suppression partially contributed by gag p24. J. Immunol. 1996; 157: 4244–4250
  • Adams G B, Pym A S, Poznansky M C, McClure M O, Weber J N. The in vivo effects of combination antiretroviral drug therapy on peripheral blood CD34+ cell colony‐forming units from HIV type 1 infected patients. AIDS Res and Human Retroviruses 1999; 15: 551–559
  • de Monye C, Karcher D S, Boelaert J R, Gordeuk V R. Bone marrow macrophage iron grade and survival of HIV‐seropositive patients. AIDS 1999; 13: 375–380
  • Voulgaropoulou F, Tan B, Soares M, Hahn B, Rat‐ner L. Distinct human immunodeficiency virus strains in the bone marrow are associated with the development of thrombocytopenia. J. Virol. 1999; 73: 3497–3504
  • Slobod K S, Bennett T A, Freiden P J, Kechli Am, Howlett N, Flynn P M, Head D R, Srivastava D K, Boyett J M, Brenner M K, Garcia J V. Mobilization of CD34+ progenitor cells by granulocyte colony‐stimulating factor in human immunodeficiency virus type 1‐infected adults. Blood 1996; 88: 3329–3335
  • Nielsen S D, Afzelius P, Dam‐larsen S, et al. Effect of granulocyte colony‐stimulating factor (G‐CSF) in human immunodeficieny virus infected patients: increase in numbers of naive CD4 cells and CD34 cells makes G‐CSF a candidate for use in gene therapy or to support antiretroviral therapy. J. Inf. Dis. 1998; 177: 1733–6
  • Schooley R T, Mladenovic J, Sevin A, Chiu S, Miles S A, Pomerantz R J, Campbell T B, Bell D, Ambruso D, Wong R, Landay A, Coombs R W, Fox L, Kamoun M, Jacovini J, ACTG 285 Study Team. A pilot study of CD34+ stem cell mobilization and harvesting from the peripheral blood of persons with HIV‐1 infection: reduced mobilization in advanced disease. J. Inf. Dis.
  • Cambell T, Sevin A, Coombs R W, Peterson G C, Rosandich M, Kuritzkes D R, Mladenovic J, Landay A, Wong R, Ambruso D, Miles S, Pomerantz R J, Schooley R T, ACTG 285 Study Team. Changes in human immunodeficiency virus type 1 virus load during mobilization and harvesting of hematopoietic progenitor cells. Blood
  • Scadden D T, Pickus Hammer SC, Stretcher B, Bresnahan J, Gere J, McGrath J, Agosti J M. Lack of in vivo effect of granulocyte‐macrophage colony‐stimulating factor on human immunodeficiency virus type 1. AIDS Res and Human Retroviruses 1996; 12: 1151–1159
  • Groopman J E, Mitsuyasu R T, DeLeo M J, Oette D H, Golde D W. Effect of recombinant human granulocyte‐macrophage colony‐stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. N. Eng. J. Med. 1997; 317: 593–598
  • Mondal D, Agrawal K C. Effect of HIV type 1 Tat protein on butyric acid‐induced differentiation in a hematopoietic progenitor cell line. AIDS Res and Human Retro‐viruses 1996; 12: 1529–1536
  • Frazier A LB, Garcia J V. Retrovirus‐mediated transfer and long‐term expression of HIV type 1 tat gene in murine hematopoietic tissues. AIDS Res and Human Retroviruses 1994; 10: 1517–1524
  • Calenda V, Graber P, Delamarter J F, Chermann J C. Involvement of HIV nef protein in abnormal hematopoiesis in AIDS: in vitro study on bone marrow progenitor cells. Eur. J. Hematol. 1994; 52: 103–107
  • Zauli G, Vitale M, Re M C, Furlini G, Zamai L, Falcieri E, Bibellini D, Visani G, Davis B R, Capitano S, LaPlaca M. In vitro exposure to human immunodeficiency virus type 1 induces apoptotic cell death of the factor dependent W‐1 hematopoietic cell‐lines. Blood 1994; 83: 167–175
  • Re M C, Furlini G, ZauIi G, LaPlaca M. Human immunodeficiency virus type 1 (HIV‐1) and human hematopoietic progenitor cells. Arch. Virol. 1994; 137: 1–23
  • Zauli G, Vitale M, Gibellini, Capitano S. Inhibition of purified CD34+ hematopoietic progenitor cells by human immunodeficiency virus 1 or gp120 mediated by endogenous transforming growth factor β1. J. Exp. Med. 1996; 183: 99–108
  • Zauli G, Re M C, Visani G, Furlini G, Mazza P, Vignoli M, LaPlaca M. Evidence for a human immunodeficiency virus type 1‐mediated suppression of uninfected hematopoietic (CD34+) cells in AIDS patients. J. Infect. Dis. 1992; 166: 710–6
  • Kaushal S, LaRussa V R, Gartner S, Kessler S, Perfetto S, Yu Z, Ritchey D W, Xu J, Perera P, Kim J, Reid T, Mayers D L, St Louis D, Mosca J D. Exposure of human CD34+ cells to human immunodeficiency virus type 1 does not influence their expansion and proliferation of hematopoietic progenitors in vitru. Blood 1996; 88: 130–137
  • Wiley E L, Nightingale S D. Opportunistic events and p17 expression in the bone marrow of human immunodeficiency virus‐infected patients. J. Infect. Dis. 1994; 169: 617–20
  • Geissler R G, Ganser A, Ottmann O G, Gute P, Morawetz A, Guba P, Helm E B, Hoelzer D. In vitro improvement of bone marrow‐derived hematopoietic colony formation in HIV‐positive patients by alpha‐D‐tocopherol and erythropoietin. Eur. J. Hematol. 1994; 53: 201–206
  • Steinberg H N, Crumpacker C S, Chatis P A. In vitro suppression of normal human bone marrow progenitor cells by human immunodeficiency virus. J. Virol. 1991; 65: 1765–1769
  • Stella C C, Ganser A, Hoelzer D. Defective in vitro growth of the hematopoietic progenitor cells in the acquired immunodeficiency syndrome. J. Clin. Invest. 1987; 80: 286–293
  • Donahue R E, Johnson M M, Zon L I, Clark S C, Groopman J E. Suppression of in vitru haematopoiesis following human immunodeficiency virus infection. Nature 1987; 326: 200–203
  • Hillyer C D, Lackey D A, Villinger F, Winton E F, McClure H M, Ansari A A. CD34+ and CFU‐Gm progenitors are significantly decreased in SIVsmm9 infected rhesus macaques with minimal evidence of direct viral infection by polymerase chain reaction. Am. J. Hematol. 1993; 43: 274
  • Kinniburgh D, Russell N H. Comparative study of CD34 positive cells and subpopulations in human umbilical cord blood and bone marrow. Bone Marrow Transplantation 1993; 12: 489–494
  • Steinberg H N, Anderson J, Crumpacker C S, Chatis P A. HIV infection of the BS‐1 human stroma cells line: effect on murine hematopoiesis. Virology 1993; 193: 524
  • Bagnara G P, Zauli G, Giovannini M, Re M C, Furlini G, LaPlaca M. Early loss of circulating hematopoietic progenitors in HIV‐1‐infected subjects. Exp. Hematol. 1990; 18: 426
  • Marandin A, Canque B, Coulombel L, Gluckman J C, Vainchenker W, Louache F. In vitro infection of bone marrow adherent cells by human immunodeficiency virus type 1 (HIV‐1) does not alter their ability to support haematopoiesis. Virology 1995; 213: 245–248
  • Hoelzer D, Ganser A. Gamma delta‐T cell receptor positive lymphocytes inhibit human hematopoietic progenitor cell growth in HIV type 1‐infected patients. AIDS Res Human Retroviruses 1996; 12: 577
  • Bahner I, Kearns K, Coutinho S, Leonard E H, Kohn D B. Infection of human marrow stroma by human immunodeficiency virus‐1 (HIV‐1) is both required and sufficient for HIV‐1‐induced hematopoietic suppression in virro: demonstration by gene modification of primary human stroma. Blood 1997; 90: 1781
  • Esser R, Glienke W, Von Briesen H, Rubsamen‐Waigmann H, Andreesen R. Differential regulation of proinflammatory and hematopoietic cytokines in human macrophages after infection with human immunodeficiency virus. Blood 1996; 88: 3474
  • Maciejewski J P, Weichold F F, Young N S. HIV‐1 suppression of hematopoiesis in vitro mediated by envelope glycoprotein and TNF‐alpha. J. Immunol. 1994; 163: 4303
  • Zauli G, Davis B R, Re M C, Visani G, Furlini G, LaPlaca M. Tat protein stimulated production of transforming growth factor β1 by marrow macrophages: A potential mechanism for human immunodeficiency virus‐1‐induced hematopoietic suppression. Blood, 80: 3036, 2992
  • Maradin A, Katz A, Oksenhendler E, et al. Loss of primitive progenitors in patients with human immunodeficiency virus infection. Blood 1996; 88: 4568–78
  • Kaczmarski R S, Davison F, Blair E, Sutherland S, Moxhan J, McManus T, Mufti G J. Detection of HIV in haematopoietic progenitors. Br. J. Haematol. 1992; 82: 764–769
  • Folks T M, Kessler S W, Orenstein J M, Justement J S, Jaffe E S, Fauci A S. Infection and replication of HIV‐1 in purified progenitor cells of normal human bone marrow. Science 1988; 242: 919–922
  • Zauli G, Vitale M, Gibellini D, Capitini S. Inhibition of purified CD34+ hematopoietic progenitor cells by human immunodeficiency virus 1 or gp120 mediated by endogenous transforming growth factor beta 1. J. Exp. Med. 1996; 183: 99
  • Alllalio G, North M, Means R T, Jr. Inhibition of marrow CFU‐E colony formation from human immunodeficiency virus infected patients by β‐ and gamma interferon. Amer. J. Hematol. 1996; 53: 118
  • Emerman M. HIV‐1, Vpr and the cell cycle. Curr. Biol. 1996; 6: 1096–1103
  • Vodicka M A, Koepp D M, Silver P A, Emerman M. HIV‐1 Vpr interacts with the nuclear transport pathway to promote macrophage infection. Genes. & Develop. 1998; 12: 175–185
  • Connor R I, Chen B K, Choe S, Landau N R. Vpr is required for efficient replication of human immunodeficiency virus type 1 in mononuclear phagocytes. Virology 1995; 206: 935–944
  • Heinzinger N, Bukrinsky M, Haggerty S, Ragland A, KewalRamani V, Lee M, Gendelman H, Ratner L, Stevenson M, Emerman M. The HIV‐I Vpr protein influences nuclear targeting of viral nucleic acids in non‐dividing cells. Proc. Natl. Acad. Sci. USA. 1994; 91: 7311–7315
  • Gallay P, Stitt V, Mundy C, Oettinger M, Trono D. Role of the karyopherin pathway in human immunodeficiency virus type 1 nuclear import. J. Virol. 1996; 70: 1027–1032
  • Rey F, BouHamdan M, Navarro J ‐M, Agostini I, Wil‐letts K, Bouyac M, Tamalet C, Spire B, Vigne R, Sire J. A role for human immunodeficiency virus type 1 Vpr during infection of peripheral blood mononuclear cells. J. Gen. Virol. 1998; 79: 1083–1087
  • Vodicka M A, Koepp D M, Silver P A, Emerman M. HIV‐1 Vpr interacts with the nuclear transport pathway to promote macrophage infection. Genes. & Develop. 1998; 12: 175–185
  • Fouchier R AM, Meyer B E, Simon J HM, Fischer U, Albright A V, Gonzalez‐Scarano F, Malim M H. Interaction of the human immunodeficiency virus type 1 Vpr protein with the nuclear pore complex. J. Virol. 1998; 72: 6004–5013
  • Popov S, Rexach M, Ratner L, Blobel G, Bukrinsky M. Viral protein R regulates docking of the HIV‐1 preintegration complex to the nuclear pore complex. J. Biol. Chem. 1998; 273: 13347–13352
  • Re E, Braaaten D, Franke E K, Luban J. Human immunodeficiency virus type 1 arrests the cell cycle in G2 by inhibiting the activation of p334cdc2‐cyclin B. J. Virol. 1995; 69: 6859–6564
  • Goh W ‐C, Roger 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. Nature Med. 1998; 4: 65–71
  • Jowett J BM, Plannelles V, Poon B, Shah N P, Chen M ‐L, Chen I SY. 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: 6304–6313
  • He J, Choe S, Walker R, DiMarzio 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: 6705–6711
  • Planelles V, Bachelerie F, Jowett J BM, Haislip A, Xie Y, Banooni P, Masuda T, Chen I SY. Fate of the human immunodeficiency virus type 1 provirus in infected cells: a role for Vpr. J. Virol. 1995; 69: 5883–5889
  • Roger 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: 882–88
  • Bartz S R, Rogel M E, Emerman M. Human immunodeficiency virus type 1 cell cycle control: Vpr is cytostatic and mediates G2 accumulation by a mechanism which differs from DNA damage checkpoint control. J. Virol. 1996; 70: 2324–2331
  • Poon B, Jowett J BM, Stewart S A, Armstrong R W, Rishton G M, Chen I SY. Human immunodeficiency virus type 1 Vpr gene induces phenotypic effects similar to those of the DNA alkylating agent, nitrogen mustard. J. Virol. 1997; 71: 3961–3971
  • Levy D N, Fernandes L S, Williams W V, Weiner D B. Induction of cell differentiation by human immunodeficiency virus 1 Vpr. Cell 1993; 72: 541–550
  • Yao X ‐J, Mouland A J, Subbramanian R A, Forget J, Rougeau N, Bergeron D, Cohen E A. Vpr stimulates viral expression and induces cell killing in human immunodeficiency virus type 1 infected dividing Jurkat T cells. J. Virol. 1998; 72: 4686–4693
  • Yao X ‐J, Subramanian R A, Rougeau N, Boisvert F, Bergeron D, Cohen E A. Mutagenic analysis of human immunodeficiency virus type 1 Vpr: Role of a predicted N‐terminal alpha‐helical structure in Vpr nuclear localization and virion incorporation. J. Virol. 1995; 69: 7032–7044
  • Kondo E, Mammano F, Cohen E A, Gottlinger H G. The p6gag domain of human immunodeficiency virus type 1 is sufficient for the incorporation of Vpr into heterologous viral particles. J. Virol. 1995; 69: 2759–2764
  • Paxton W, Connor R I, Landau N R. Incorporation of Vpr into human immunodeficiency virus type 1 virions: Requirement for the p6 region of gag and mutational analysis. J. Virol. 1993; 67: 7229–7237
  • Felzien L K, Woffendin C, Hottiger M O, Subbramanian R A, Cohen E A, Nabel G J. HIV transcriptional activation by the accessory protein, Vpr, is mediated by the p300 co‐activator. Proc. Natl. Acad. Sci. USA. 1998; 95: 5281–5286
  • Hrimechi M, Yao X ‐J, Bachand F, Rougeau N, Cohen E A. Human immunodeficiency virus type 1 (HIV‐1) Vpr functions as a immediate early protein during HIV‐1 infection. J. Virol. 1999; 73: 4101–4109
  • Levy D N, Refaeli Y, Weiner D B. Extracellular Vpr protein increases cellular permissiveness to human immunodeficiency virus replication and reactivates virus from latency. J. Virol. 1995; 69: 1243–1252
  • Levy D N, Refaeli Y, MacGregor R R, Weiner D B. Serum Vpr regulates productive infection and latency of human immunodeficiency virus type 1. Proc. Natl. Acad. Sci. USA. 1994; 91: 10873–10877
  • Refaeli Y, Levy D N, Weiner D B. The glucocorticoid receptor type II complex is a target of the HIV‐1 Vpr gene product. Proc. Natl. Acad. Sci. USA. 1995; 92: 3621–3625
  • Bouhamdan M, Benichou S, Rey F, Navmo J ‐M, Agostini I, Spire B, Camonis J, Slupphaug G, Vigne R, Benarous R, Sire J. Human immunodeficiency virus type 1 Vpr protein binds to the uracil DNA glycosy‐lase DNA repair enzyme. J. Virol. 1996; 70: 697–704
  • Gragerov A, Kino T, Ilyin‐Gragerova G, Chrousos G P, Pavlakis G N. HHR23A, the human homologue of the yeast repair protein RAD23, interacts specifically with Vpr protein and prevents cell cycle arrest but not the transcriptional effects of Vpr. Virology 1998; 245: 323–330
  • Zhou Y, Lu Y, Ratner L. Arginine residues in the C‐terminus of HIV‐1 Vpr are important for nuclear localization and cell cycle arrest. Virology 1998; 242: 414–424
  • Mahalingam S, Khan S A, Jabbar M A, Monken C E, Collman R G, Srinivasan A. Identification of residues in the N‐terminal acidic domain of HIV‐1 Vpr essential for virion incorporation. Virology 1995; 207: 297–302
  • DiMarzio P, Choe S, Ebright M, Knoblauch R, Landau N R. Mutational analysis of cell cycle arrest, nuclear localization and virion packaging of human immunodeficiency virus type 1 Vpr. J. Virol. 1995; 69: 7909–7916
  • Macreadie I G, Castelli L A, Hewish D R, Kirkpatrick A, Ward A C, Azad A A. A domain of human immunodeficiency virus type 1 Vpr containing repeated H(S/F)RIG amino acid motif causes cell growth arrest and structural defects. Proc. Natl. Acad. Sci. USA. 1995; 92: 2770–2774
  • Mahalingam S, Patel M, Collman R G, Srinivasan A. The carboxy‐terminal domain is essential for stability and not for virion incorporation of HIV‐1 Vpr into virus particles. Virology 1995; 214: 647–452
  • Mahalingam S, Collman R G, Patel M, Monken C E, Srinivasan A. Role of the conserved dipeptide Gly75 and Cys76 on HIV‐1 Vpr function. Virology 1995; 210: 495–500
  • Nie Z, Bergeron D, Subbramanian R A, Yao X ‐J, Checroune F, Rougeau N, Cohen E A. The putative alpha helix 2 of human immunodeficiency virus type 1 Vpr contains a determinant which is responsible for the nuclear translocation of proviral DNA in growth‐arrested cells. J. Virol. 1998; 72: 4104–4115
  • Poon B, Grovit‐Ferbas K, Stewart S A, Chen I SY. Cell cycle arrest by Vpr in HIV‐1 virions and insensitivity to antiretroviral agents. Science 1998; 281: 266–270
  • Zhao Y, Cao J, O'Gorman M RG, Yu M, Yogev R. Effect of human immunodeficiency virus type 1 protein R (Vpr) gene expression on basic cellular function of fission yeast schizosaccharomyces pombe. J. Virol. 1996; 70: 5821–5826
  • Zhao Y, Yu M, Chen M, Elder R T, Yamamoto A, Cao J. Pleiotropic effects of HIV‐1 protein R (Vpr) on morphogenesis and cell survival in fission yeast and antagonism by pentoxifylline. Virology 1998; 246: 266–276
  • Stewart S A, Poon B, Jowett J BM, Chen I SY. Human immunodeficiency virus Vpr induces apoptosis following cell cycle arrest. J. Virol. 1997; 71: 5579–5592
  • Conti L, Rainaldi G, Matarrese P, Varano B, Rivabene R, Columba S, Sato A, Belardelli F, Malorni W, Gessani S. The HIV‐1 Vpr protein acts as a negative regulatory of apoptosis in a human lymphoblastoid T cell line: Possible implications for the pathogenesis of AIDS. J. Exp. Med. 1998; 187: 403–413
  • Ayyavoo V, Mahboubi A, Mahalingam S, Ramdingam R, Kudchodkax S, Williams W V, Green D R, Weiner D B. HIV‐1 Vpr suppresses immune activation and apoptosis through regulation of nuclear factor kB. Nature Med. 1997; 3: 1117–1123
  • Lamb R A, Pinto L H. Do Vpu and Vpr of human immunodeficiency virus type 1 and NB of influenza B virus have ion channel activities in the viral life‐cycles?. Virology 1997; 229: 1–11
  • Piller S C, Ewart G D, Premkumar A, Cox G B, Gage P W. Vpr protein of human immunodeficiency virus type 1 forms cation‐selective channels in planar lipid bilayers. Proc. Natl. Acad. Sci. USA. 1996; 93: 111–115
  • Piller S C, Ewart G D, Jans D A, Gage P W, Cox G B. The amino‐terminal region of Vpr from human immunodeficiency virus type 1 forms ion channels and kills neurons. J. Virol. 1999; 73: 4230–4238
  • Wu X, Liu H, Xiao H, Kim J, Seshaiah P, Natsoulis G, Boeke J D, Hahn B H, Kappes J C. Targeting foreign proteins to human immunodeficiency virus particles via fusion with Vpr and Vpx. J. Virol. 1995; 69: 3389–3398
  • Fletcher T M, Soares M A, McPhearson S, Hui H, Wiskerchen M A, Muesing M A, Shaw G M, Leavitt A D, Boeke J D, Hahn B H. Complementation of inte‐grase function in HIV‐I virions. EMBO J. 1997; 16: 5123–5138
  • Wu X, Liu H, Xiao H, Conway J A, Hunter E, Kappes J C. Functional R. T. and IN incorporated into HIV‐I particles independently of the GagPol precursor protein. EMBO J. 1997; 16: 5113–5122
  • Wu X, Liu H, Xiao H, Conway J A, Kappes J C. Inhibition of human and simian immunodeficiency virus protease function by targeting Vpx‐protease‐mutant fusion protein into viral particles. J. Viol. 1996; 3378–3384
  • Duan L ‐X, Oakes J, Ferraro A, Bagasra O, Pomerantz R J. Tat and rev affect replication of human immunodeficiency virus type 1 in various cells. Viology 1994; 199: 474
  • Pereira R, Halford K W, O'Hara M, Leeper D B, Sokolov B P, Pollard M D, Bagasra O, Prockop D J. Cultured adherent cells from marrow can serve as long‐lasting precursor cells for bone, cartilage and lung in irradiated mice. Proc. Natl. Acad. Sci. USA 1995; 92: 4857
  • Tomida M. Mononuclear Phagocytes: Physiology and Pathology, R T Dean, W Jessup. Elsevier, Amsterdam 1985; 243
  • Turpin J, Lopez‐Berestein G. Mononuclear Phagocytes. Cell Biology, G Lopez‐Berestein, J Klostergaard. CRC Press, Boca Raton 1993; 71
  • Kulkosky J, Laptev A, Shetty S, Srinivasan A, BouHamdan M, Prockop D J, Pomerantz R J. HIV‐1 Vpr alters bone marrow cell function. Blood 1999; 93: 1906–1915
  • Cen D, Zauli G, Szarnicki R, Davis B R. Effect of different human immunodeficiency virus type‐1 (HIV‐1) isolates on long‐term bone marrow haemopoiesis. Brit. J. of Haemat., 85: 596–602
  • Harbol A W, Liesveld J L, Simpsom‐Haidaris J, Abboud C N. Mechanisms of cytopenia in human immunodeficiency virus infection. Blood Rev. 1994; 8: 241
  • Gowda S D, Stein B S, Mohagheghpour N, Benike C J, Engleman E G. Evidence that T cell activation is required for HIV‐1 entry in CD4+ lymphocytes. J. Immunol. 1989; 142: 773
  • Connor R I, Chen B K, Choe S, Landau N R. Vpr is required for efficient replication of human immunodeficiency virus type‐1 in mononuclear phagocytes. Virology 1995; 206: 935
  • 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: 8080
  • Campbell B J, Hirsch V. Vpr of simian immunodeficiency virus of African green monkeys is required for replication in macaque macrophages and lymphocytes. J. Virol. 1997; 71: 5593

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.