HIV-1-Derived Lentiviral Vectors

  • L. E. Ailles
  • L. Naldini
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 261)


The primary vectors of choice for gene therapy applications have been oncoretroviruses due to their simple genetic organization and their ability to integrate into the host cell genome without incurring cellular toxicity (ANDERSON 1998). However, these vectors require cell division for integration to occur (MILLER et al. 1990) due to a requirement for nuclear envelope breakdown to allow entry of the viral integration complex into the nucleus (ROE et al. 1993). This presents a major obstacle for in vivo or ex vivo transduction of non-dividing cells such as neurons, hepatocytes, muscle fibres, quiescent lymphocytes, and haematopoietic stem cells, as these cells are either inaccessible by such vectors, or must be manipulated in potentially detrimental ways to facilitate cell division and vector integration. For this reason, interest in recent years has turned to lentiviruses, due to their ability to infect and integrate in certain types of non-dividing cells (WEINBERG et al. 1991; BUKRINSKY et al. 1993; LEWIS and EMERMAN 1994). One lentivirus on which much work has been focused to derive vectors for gene therapy has been HIV-1, as it is the best characterized of the lentiviruses. The remainder of this review will focus on the properties of HIV-1 that allow it to efficiently infect non-dividing cells, and on the development of progressively safer and more efficient HIV-1-derived vectors over the past few years.


Nuclear Import Transfer Vector Nondividing Cell Human Immunode Woodchuck Hepatitis Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aiken C (1997) Pseudotyping human immunodeficiency virus type 1 (HIV-1) by the glycoprotein of vesicular stomatitis virus targets HIV-1 entry to an endocytic pathway and suppresses both the requirement for Nef and the sensitivity to cyclosporin A. J Virol 71:5871–5877PubMedGoogle Scholar
  2. Aiken C, Trono D (1995) Nef stimulates human immunodeficiency virus type 1 proviral DNA synthesis. J Virol 69:5048–5056PubMedGoogle Scholar
  3. Anderson WF (1998) Human Gene Ther Nature 392:25–30Google Scholar
  4. Arya SK, Zamani M, Kundra P (1998) Human immunodeficiency virus type 2 lentivirus vectors for gene transfer: expression and potential for helper virus-free packaging. Hum Gene Ther 9:1371–1380PubMedGoogle Scholar
  5. Bartz SR, Emerman M (1999) Human immunodeficiency virus type 1 Tat induces apoptosis and increases sensitivity to apoptotic signals by up-regulating FLICE/caspase-8. J Virol 73:1956–1963PubMedGoogle Scholar
  6. Bartz SR, Vodicka MA (1997) Production of high-titer human immunodeficiency virus type 1 pseudo-typed with vesicular stomatitis virus glycoprotein. Methods 12:337–342PubMedGoogle Scholar
  7. Bensadoun JC, Deglon N, Tseng JL, Ridet JL, Zum AD, Aebischer P (2000) Lentiviral vectors as a gene delivery system in the mouse midbrain: cellular and behavioral improvements in a 6-OHDA model of Parkinson’s disease using GDNF. Exp Neurol 164:15–24PubMedGoogle Scholar
  8. Binley J, Moore JP (1997) HIV-cell fusion. The viral mousetrap. Nature 387:346–348PubMedGoogle Scholar
  9. Blomer U, Naldini L, Kafri T, Trono D, Verma IM, Gage FH (1997) Highly efficient and sustained gene transfer in adult neurons with a lentivirus vector. J Virol 71:6641–6649PubMedGoogle Scholar
  10. Bosch A, Perret E, Desmaris N, Trono D, Heard JM (2000) Reversal of pathology in the entire brain of mucopolysaccharidosis type VII mice after lentivirus-mediated gene transfer. Hum Gene Ther 11:1139–1150PubMedGoogle Scholar
  11. Bukovsky AA, Song JP, Naldini L (1999) Interaction of human immunodeficiency virus-derived vectors with wild-type virus in transduced cells. J Virol 73:7087–7092PubMedGoogle Scholar
  12. Bukovsky A, Dull T, Follenzi A, Nguyen M, Kelly M, McGuinness R, Malech H, Naldini L (2000) Novel design of HIV-based vector system with no viral sequences overlap between packaging and transfer vector constructs. Mol Ther 1:S139Google Scholar
  13. Bukrinsky MI, Haffar OK (1999) HIV-1 nuclear import: in search of a leader. Front Biosci 4:772–781Google Scholar
  14. Bukrinsky MI, Haggerty S, Dempsey MP, Sharova N, Adzhubel A, Spitz L, Lewis P, Goldfarb D, Emerman M, Stevenson M (1993) A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature 365:666–669PubMedGoogle Scholar
  15. Bukrinsky MI, Sharova N, Dempsey MP, Stanwick TL, Bukrinskaya AG, Haggerty S, Stevenson M (1992) Active nuclear import of human immunodeficiency virus type 1 preintegration complexes. Proc Natl Acad Sci USA 89:6580–6584PubMedGoogle Scholar
  16. Burns JC, Friedmann T, Driever W, Burrascano M, Yee JK (1993) Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titre and efficient gene transfer into mammalian and nonmammalian cells. Proc Natl Acad Sci USA 90:8033–8037PubMedGoogle Scholar
  17. Cassan M, Delaunay N, Vaquero C, Rousset JP (1994) Translational frameshifting at the gag-pol junction of human immunodeficiency virus type 1 is not increased in infected T-lymphoid cells. J Virol 68:1501–1508PubMedGoogle Scholar
  18. Chameau P, Mirambeau G, Roux P, Paulous S, Buc H, Clavel F (1994) HIV-1 reverse transcription. A termination step at the center of the genome. J Mol Biol 241:651–662Google Scholar
  19. Chinnasamy D, Chinnasamy N, Enriquez MJ, Otsu M, Morgan RA, Candotti F (2000) Lentiviral-mediated gene transfer into human lymphocytes: role of HIV-1 accessory proteins. Blood 96:1309–1316PubMedGoogle Scholar
  20. Clapham PR, Weiss RA (1997) Immunodeficiency viruses. Spoilt for choice of co-receptors. Nature 388:230–231PubMedGoogle Scholar
  21. Clever JL, Parslow TG (1997) Mutant human immunodeficiency virus type 1 genomes with defects in RNA dimerization or encapsidation. J Virol 71:3407–3414PubMedGoogle Scholar
  22. Coffin J, Hughes SH, Varmus HE (2000) Retroviruses. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.Google Scholar
  23. Consiglio A, Quattrini A, Martino S, Bensadoun JC, Dolcetta D, Trojani A, Benaglia G, Marchesini S, Cestari V, Oliverio A, Bordignon C, Naldini L (2001) In vivo gene therapy of metachromatic leukodystrophy in lentiviral vectors: correlation of neuropathology and protection against learning impairments in affected mice. Nat Med 7:310–316PubMedGoogle Scholar
  24. Corbeau P, Kraus G, Wong-Staal F (1998) Transduction of human macrophages using a stable HIV-1/HIV-2-derived gene delivery system. Gene Ther 5:99–104PubMedGoogle Scholar
  25. Costello E, Munoz M, Buetti E, Meylan PR, Diggelmann H, Thali M (2000) Gene transfer into stimulated and unstimulated T lymphocytes by HIV-1-derived lentiviral vectors. Gene Ther 7:596–604PubMedGoogle Scholar
  26. Cullen BR (1998) HIV-1 auxiliary proteins: making connections in a dying cell. Cell 93:685–692PubMedGoogle Scholar
  27. Dalgleish AG, Beverley PC, Clapham PR, Crawford DH, Greaves MF, Weiss RA (1984) The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312:763–767PubMedGoogle Scholar
  28. Deglon N, Tseng JL, Bensadoun JC, Zum AD, Arsenijevic Y, Pereira DA, Zufferey R, Trono D, Aebischer P (2000) Self-inactivating lentiviral vectors with enhanced transgene expression as potential gene transfer system in Parkinson’s disease. Hum Gene Ther 11:179–190PubMedGoogle Scholar
  29. Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill CM, Davis CB, Peiper SC, Schall TJ, Littman DR, Landau NR (1996) Identification of a major co-receptor for primary isolates of HIV-1. Nature 381:661–666PubMedGoogle Scholar
  30. Deng HK, Unutmaz D, KewalRamani VN, Littman DR (1997) Expression cloning of new receptors used by simian and human immunodeficiency viruses. Nature 388:296–300PubMedGoogle Scholar
  31. Dettenhofer M, Cen S, Carlson BA, Kleiman L, Yu XF (2000) Association of human immunodeficiency virus type 1 Vif with RNA and its role in reverse transcription. J Virol 74:8938–8945PubMedGoogle Scholar
  32. Dull T, Zufferey R, Kelly M, Mandel RJ, Nguyen M, Trono D, Naldini L (1998) A third-generation lentivirus vector with a conditional packaging system. J Virol 72:8463–8471PubMedGoogle Scholar
  33. Emerman M (2000) Learning from lentiviruses. Nat Genet 24:8–9PubMedGoogle Scholar
  34. Emerman M, Malim MH (1998) HIV-1 regulatory/accessory genes: keys to unraveling viral and host cell biology. Science 280:1880–1884PubMedGoogle Scholar
  35. Federico M (1999) Lentiviruses as gene delivery vectors. Curr Opin Biotechnol 10:448–453PubMedGoogle Scholar
  36. Feng Y, Broder CC, Kennedy PE, Berger EA (1996a) HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272:872–877PubMedGoogle Scholar
  37. Feng YX, Copeland TD, Henderson LE, Gorelick RJ, Bosche WJ, Levin JG, Rein A (1996b) HIV-1 nucleocapsid protein induces “maturation” of dimeric retroviral RNA in vitro. Proc Natl Acad Sci USA 93:7577–7581PubMedGoogle Scholar
  38. Follenzi A, Ailles LE, Bakovic S, Geuna M, Naldini L (2000) Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences. Nat Genet 25:217–222PubMedGoogle Scholar
  39. Fouchier RA, Meyer BE, Simon JH, Fischer U, Albright AV, Gonzalez-Scarano F, Malim MH (1998) Interaction of the human immunodeficiency virus type 1 Vpr protein with the nuclear pore complex. J Virol 72:6004–6013PubMedGoogle Scholar
  40. Frankel AD, Young JA (1998) HIV-1: fifteen proteins and an RNA. Ann Rev Biochem 67:1–25PubMedGoogle Scholar
  41. Freed EO, Martin MA (1994)HIV-1 infection of non-dividing cells. Nature 369:107–108PubMedGoogle Scholar
  42. 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 USA 94:9825–9830PubMedGoogle Scholar
  43. 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 70:1027–1032PubMedGoogle Scholar
  44. Gallichan WS, Kafri T, Krahl T, Verma IM, Sarvetnick N (1998) Lentivirus-mediated transduction of islet grafts with interleukin 4 results in sustained gene expression and protection from insulitis. Hum Gene Ther 9:2717–2726PubMedGoogle Scholar
  45. Gasmi M, Glynn J, Jin MJ, Jolly DJ, Yee JK, Chen ST (1999) Requirements for efficient production and transduction of human immunodeficiency virus type 1-based vectors. J Virol 73:1828–1834PubMedGoogle Scholar
  46. Goh WC, Rogel ME, Kinsey CM, Michael SF, Fultz PN, Nowak MA, Hahn BH, 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 4:65–71PubMedGoogle Scholar
  47. Grande A, Piovani B, Aiuti A, Ottolenghi S, Mavilio F, Ferrari G (1999) Transcriptional targeting of retroviral vectors to the erythroblastic progeny of transduced hematopoietic stem cells. Blood 93:3276–3285PubMedGoogle Scholar
  48. Guenechea G, Gan OI, Inamitsu T, Dorrell C, Pereira DS, Kelly M, Naldini L, Dick JE (2000) Transduction of human CD34+ CD38-bone marrow and cord blood-derived SCID-repopulating cells with third-generation lentiviral vectors. Mol Ther 1:566–573PubMedGoogle Scholar
  49. He J, Choe S, Walker R, Di Marzio P, Morgan DO, Landau NR (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 69:6705–6711PubMedGoogle Scholar
  50. Hill CM, Deng H, Unutmaz D, KewalRamani VN, Bastiani L, Gorny MK, Zolla-Pazner S, Littman DR (1997) Envelope glycoproteins from human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus can use human CCR5 as a coreceptor for viral entry and make direct CD4-dependent interactions with this chemokine receptor. J Virol 71:6296–6304PubMedGoogle Scholar
  51. Hill CP, Worthylake D, Bancroft DP, Christensen AM, Sundquist WI (1996) Crystal structures of the trimeric human immunodeficiency virus type 1 matrix protein: implications for membrane association and assembly. Proc Natl Acad Sci USA 93:3099–3104PubMedGoogle Scholar
  52. Kafri T, Blomer U, Peterson DA, Gage FH, Verma IM (1997) Sustained expression of genes delivered directly into liver and muscle by lentiviral vectors. Nat Genet 17:314–317PubMedGoogle Scholar
  53. Kanki PJ, Travers KU, MBoup S, Hsieh CC, Marlink RG, Gueye-NDiaye A, Siby T, Thior I, Hernandez-Avila M, Sankale JL (1994) Slower heterosexual spread of HIV-2 than HIV-1. Lancet 343:943–946PubMedGoogle Scholar
  54. Katz RA, Skalka AM (1994) The retroviral enzymes. Ann Rev Biochem 63:133–173PubMedGoogle Scholar
  55. Kerkau T, Bacik I, Bennink JR, Yewdell JW, Hunig T, Schimpl A, Schubert U (1997) The human immunodeficiency virus type 1 (HIV-1) Vpu protein interferes with an early step in the biosynthesis of major histocompatibility complex (MHC) class I molecules. J Exp Med 185:1295–1305PubMedGoogle Scholar
  56. Kim VN, Mitrophanous K, Kingsman SM, Kingsman AJ (1998) Minimal requirement for a lentivirus vector based on human immunodeficiency virus type 1. J Virol 72:811–816PubMedGoogle Scholar
  57. Kinoshita S, Chen BK, Kaneshima H, Nolan GP (1998) Host control of HIV-1 parasitism in T cells by the nuclear factor of activated T cells. Cell 95:595–604PubMedGoogle Scholar
  58. Kondo E, Gottlinger HG (1996) A conserved LXXLF sequence is the major determinant in p6gag required for the incorporation of human immunodeficiency virus type 1 Vpr. J Virol 70:159–164PubMedGoogle Scholar
  59. Kordower JH, Bloch J, Ma SY, Chu Y, Palfi S, Roitberg BZ, Emborg M, Hantraye P, Deglon N, Aebischer P (1999) Lentiviral gene transfer to the nonhuman primate brain.Exp Neurol 160:1–16PubMedGoogle Scholar
  60. Kordower JH, Emborg ME, Bloch J, Ma SY, Chu Y, Leventhal L, McBride J, Chen E-Y, Palfi S, Roitberg BZ, Brown WD, Holden JE, Pyzalski R, Taylor MD, Carvey P, Ling Z, Trono D, Hantraye P, Deglon N, Aebischer P (2000) Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson’s disease. Science 290:767–773PubMedGoogle Scholar
  61. Korin YD, Zack JA (1998) Progression to the Gib phase of the cell cycle is required for completion of human immunodeficiency virus type 1 reverse transcription in T cells. J Virol 72:3161–3168PubMedGoogle Scholar
  62. Korin YD, Zack JA (1999) Nonproductive human immunodeficiency virus type 1 infection in nucleoside-treated G0 lymphocytes. J Virol 73:6526–6532PubMedGoogle Scholar
  63. Lamb RA, Pinto LH (1997) 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 229:1–11PubMedGoogle Scholar
  64. Landau NR, Page KA, Littman DR (1991) Pseudotyping with human T-cell leukemia virus type I broadens the human immunodeficiency virus host range. J Virol 65:162–169PubMedGoogle Scholar
  65. Lewis PF, Emerman M (1994) Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus. J Virol 68:510–516PubMedGoogle Scholar
  66. Madani N, Kabat D (1998) An endogenous inhibitor of human immunodeficiency virus in human lymphocytes is overcome by the viral Vif protein. J Virol 72:10251–10255PubMedGoogle Scholar
  67. Malim MH, Hauber J, Le SY, Maizel JV, Cullen BR (1989) The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature 338: 254–257PubMedGoogle Scholar
  68. Mangasarian A, Foti M, Aiken C, Chin D, Carpentier JL, Trono D (1997a) The HIV-1 Nef protein acts as a connector with sorting pathways in the Golgi and at the plasma membrane. Immunity 6:67–77PubMedGoogle Scholar
  69. Mangasarian A, Trono D (1997b) The multifaceted role of HIV Nef. Res Virol pp 30–33Google Scholar
  70. Marlink R, Kanki P, Thior I, Travers K, Eisen G, Siby T, Traore I, Hsieh CC, Dia MC, Gueye EH (1994) Reduced rate of disease development after HIV-2 infection as compared to HIV-1. Science 265:1587–1590PubMedGoogle Scholar
  71. May C, Rivella S, Callegari J, Heller G, Gaensler KM, Luzzatto L, Sadelain M (2000) Therapeutic haemoglobin synthesis in beta-thalassaemic mice expressing lentivirus-encoded human beta-globin. Nature 406:82–86PubMedGoogle Scholar
  72. Miller DG, Adam MA, Miller AD (1990) Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol Cell Biol 10:4239–4242PubMedGoogle Scholar
  73. Miyoshi H, Blomer U, Takahashi M, Gage FH, Verma IM (1998) Development of a self-inactivating lentivirus vector. J Virol 72:8150–8157PubMedGoogle Scholar
  74. Miyoshi H, Smith KA, Mosier DE, Verma IM, Torbett BE (1999) Transduction of human CD34+ cells that mediate long-term engraftment of NOD/SCID mice by HIV vectors. Science 283:682–686PubMedGoogle Scholar
  75. Miyoshi H, Takahashi M, Gage FH, Verma IM (1997) Stable and efficient gene transfer into the retina using an HIV-based lentiviral vector. Proc Natl Acad Sci USA 94:10319–10323PubMedGoogle Scholar
  76. Naldini L (1998) Lentiviruses as gene transfer agents for delivery to non-dividing cells. Curr Opin Biotechnol 9:457–463PubMedGoogle Scholar
  77. Naldini L, Blomer U, Gage FH, Trono D, Verma IM (1996a) Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proc Natl Acad Sci USA 93:11382–11388PubMedGoogle Scholar
  78. Naldini L, Blomer U, Gallay P, Ory D, Mulligan R, Gage FH, Verma IM, Trono D (1996b) In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272: 263–267PubMedGoogle Scholar
  79. Neville M, Stutz F, Lee L, Davis LI, Rosbash M (1997) The importin-beta family member Crmlp bridges the interaction between Rev and the nuclear pore complex during nuclear export. Curr Biol 7:767–775PubMedGoogle Scholar
  80. Page KA, Landau NR, Littman DR (1990) Construction and use of a human immunodeficiency virus vector for analysis of virus infectivity. J Virol 64:5270–5276PubMedGoogle Scholar
  81. Park F, Ohashi K, Kay MA (2000) Therapeutic levels of human factor VIII and IX using HIV-1-based lentiviral vectors in mouse liver. Blood 96:1173–1176PubMedGoogle Scholar
  82. Parolin C, Dorfman T, Palu G, Gottlinger H, Sodroski J (1994) Analysis in human immunodeficiency virus type 1 vectors of cis-acting sequences that affect gene transfer into human lymphocytes. J Virol 68:3888–3895PubMedGoogle Scholar
  83. Poeschla E, Corbeau P, Wong-Staal F (1996) Development of HIV vectors for anti-HIV gene therapy. Proc Natl Acad Sci USA 93:11395–11399PubMedGoogle Scholar
  84. Poeschla E, Gilbert J, Li X, Huang S, Ho A, Wong-Staal F (1998) Identification of a human immunodeficiency virus type 2 (HIV-2) encapsidation determinant and transduction of nondividing human cells by HIV-2-based lentivirus vectors. J Virol 72:6527–6536PubMedGoogle Scholar
  85. Popov S, Rexach M, Zybarth G, Reiling N, Lee MA, Ratner L, Lane CM, Moore MS, Blobel G, Bukrinsky M (1998) Viral protein R regulates nuclear import of the HIV-1 pre-integration complex. EMBO J 17:909–917PubMedGoogle Scholar
  86. Roe T, Reynolds TC, Yu G, Brown PO (1993) Integration of murine leukemia virus DNA depends on mitosis. EMBO J 12:2099–2108PubMedGoogle Scholar
  87. Schneider R, Campbell M, Nasioulas G, Felber BK, Pavlakis GN (1997) Inactivation of the human immunodeficiency virus type 1 inhibitory elements allows Rev-independent expression of Gag and Gag/protease and particle formation. J Virol 71:4892–4903PubMedGoogle Scholar
  88. Schubert U, Anton LC, Bacik I, Cox JH, Bour S, Bennink JR, Orlowski M, Strebel K, Yewdell JW (1998) CD4 glycoprotein degradation induced by human immunodeficiency virus type 1 Vpu protein requires the function of proteasomes and the ubiquitin-conjugating pathway. J Virol 72:2280–2288PubMedGoogle Scholar
  89. Schwartz O, Marechal V, Danos O, Heard JM (1995) Human immunodeficiency virus type 1 Nef increases the efficiency of reverse transcription in the infected cell. J Virol 69:4053–4059PubMedGoogle Scholar
  90. Simon JH, Malim MH (1996) The human immunodeficiency virus type 1 Vif protein modulates the postpenetration stability of viral nucleoprotein complexes. J Virol 70:5297–5305PubMedGoogle Scholar
  91. Stevenson M (2000) HIV nuclear import: What’s the flap? Nat Med 6:626–628PubMedGoogle Scholar
  92. Takahashi M, Miyoshi H, Verma IM, Gage FH (1999) Rescue from photoreceptor degeneration in the rd mouse by human immunodeficiency virus vector-mediated gene transfer. J Virol 73:7812–7816PubMedGoogle Scholar
  93. Tiganos E, Yao XJ, Friborg J, Daniel N, Cohen EA (1997) Putative alpha-helical structures in the human immunodeficiency virus type 1 Vpu protein and CD4 are involved in binding and degradation of the CD4 molecule. J Virol 71:4452–4460PubMedGoogle Scholar
  94. Unutmaz D, KewalRamani VN, Marmon S, Littman DR (1999) Cytokine signals are sufficient for HIV-1 infection of resting human T lymphocytes. J Exp Med 189:1735–1746PubMedGoogle Scholar
  95. Valentin A, Aldrovandi G, Zolotukhin AS, Cole SW, Zack JA, Pavlakis GN, Felber BK (1997) Reduced viral load and lack of CD4 depletion in SCID-hu mice infected with Rev-independent clones of human immunodeficiency virus type 1. J Virol 71:9817–9822PubMedGoogle Scholar
  96. Vigna E, Naldini L (2000) Lentiviral vectors: excellent tools for experimental gene transfer and promising candidates for gene therapy. J Gene Med 2:308–316PubMedGoogle Scholar
  97. Vodicka MA, Koepp DM, Silver PA, Emerman M (1998) HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection. Genes Dev 12:175–185PubMedGoogle Scholar
  98. von Schwedler UK, Stemmler TL, Klishko VY, Li S, Albertine KH, Davis DR, Sundquist WI (1998) Proteolytic refolding of the HIV-1 capsid protein amino-terminus facilitates viral core assembly. EMBO J 17:1555–1568Google Scholar
  99. Weinberg JB, Matthews TJ, Cullen BR, Malim MH (1991) Productive human immunodeficiency virus type 1 (HIV-1) infection of nonproliferating human monocytes. J Exp Med 174:1477–1482PubMedGoogle Scholar
  100. Wilcox DA, Olsen JC, Ishizawa L, Griffith M, White GC (1999) Integrin alphallb promoter-targeted expression of gene products in megakaryocytes derived from retrovirus-transduced human hematopoietic cells. Proc Natl Acad Sci USA 96:9654–9659PubMedGoogle Scholar
  101. Willey RL, Maldarelli F, Martin MA, Strebel K (1992) Human immunodeficiency virus type 1 Vpu protein induces rapid degradation of CD4. J Virol 66:7193–7200PubMedGoogle Scholar
  102. Wyatt R, Sodroski J (1998) The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science 280:1884–1888PubMedGoogle Scholar
  103. Zack JA, Arrigo SJ, Weitsman SR, Go AS, Haislip A, Chen IS (1990) HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. Cell 61:213–222PubMedGoogle Scholar
  104. Zack JA, Haislip AM, Krogstad P, Chen IS (1992) Incompletely reverse-transcribed human immunodeficiency virus type 1 genomes in quiescent cells can function as intermediates in the retroviral life cycle. J Virol 66:1717–1725PubMedGoogle Scholar
  105. Zennou V, Petit C, Guetard D, Nerhbass U, Montagnier L, Chameau P (2000) HIV-1 genome nuclear import is mediated by a central DNA flap. Cell 101:173–185PubMedGoogle Scholar
  106. Zufferey R, Donello JE, Trono D, Hope TJ (1999) Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors. J Virol 73: 2886–2892PubMedGoogle Scholar
  107. Zufferey R, Dull T, Mandel RJ, Bukovsky A, Quiroz D, Naldini L, Trono D (1998) Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J Virol 72:9873–9880PubMedGoogle Scholar
  108. Zufferey R, Nagy D, Mandel RJ, Naldini L, Trono D (1997) Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat Biotechnol 15:871–875PubMedGoogle Scholar
  109. zur Megede J, Chen MC, Doe B, Schaefer M, Greer CE, Selby M, Otten GR, Barnett SW (2000) Increased expression and immunogenicity of sequence-modified human immunodeficiency virus type 1 gag gene. J Virol 74:2628–2635PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • L. E. Ailles
    • 1
  • L. Naldini
    • 1
  1. 1.Laboratory for Gene Transfer and TherapyInstitute for Cancer Research and Treatment, University of Torino Medical SchoolCandiolo (Torino)Italy

Personalised recommendations