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. 1995 Apr;69(4):2058–2067. doi: 10.1128/jvi.69.4.2058-2067.1995

Human immunodeficiency virus type 1 Vif- mutant particles from restrictive cells: role of Vif in correct particle assembly and infectivity.

A M Borman 1, C Quillent 1, P Charneau 1, C Dauguet 1, F Clavel 1
PMCID: PMC188871  PMID: 7884851

Abstract

Disruption of the vif gene of human immunodeficiency virus (HIV) type 1 affects virus infectivity to various degrees, depending on the T-cell line used. We have concentrated our studies on true phenotypic Vif- mutant particles produced from CEMx174 or H9 cells. In a single round of infection, Vif- virus is approximately 25 (from CEMx174 cells) to 100 (from H9 cells) times less infectious than wild-type virus produced from these cells or than the Vif- mutant produced from HeLa cells. Vif- virions recovered from restrictive cells, but not from permissive cells, are abnormal both in terms of morphology and viral protein content. Notably, they contain much reduced quantities of envelope proteins and altered quantities of Gag and Pol proteins. Although wild-type and Vif- virions from restrictive cells contain similar quantities of viral RNA, no viral DNA synthesis was detectable after acute infection of target cells with phenotypically Vif- virions. To examine the possible role of Vif in viral entry, attempts were made to rescue the Vif- defect in H9 cells by pseudotyping Vif+ and Vif- HIV particles with amphotropic murine leukemia virus envelope. Vif- particles produced in the presence of HIV envelope could not be propagated when pseudotyped. In contrast, when only the murine leukemia virus envelope was present, significant propagation of Vif- HIV particles could be detected. These results demonstrate that Vif is required for proper assembly of the viral particle and for efficient HIV Env-mediated infection of target cells.

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Selected References

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  1. Adachi A., Gendelman H. E., Koenig S., Folks T., Willey R., Rabson A., Martin M. A. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J Virol. 1986 Aug;59(2):284–291. doi: 10.1128/jvi.59.2.284-291.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ahmad N., Venkatesan S. Nef protein of HIV-1 is a transcriptional repressor of HIV-1 LTR. Science. 1988 Sep 16;241(4872):1481–1485. doi: 10.1126/science.3262235. [DOI] [PubMed] [Google Scholar]
  3. Blanc D., Patience C., Schulz T. F., Weiss R., Spire B. Transcomplementation of VIF- HIV-1 mutants in CEM cells suggests that VIF affects late steps of the viral life cycle. Virology. 1993 Mar;193(1):186–192. doi: 10.1006/viro.1993.1114. [DOI] [PubMed] [Google Scholar]
  4. Chakrabarti L., Guyader M., Alizon M., Daniel M. D., Desrosiers R. C., Tiollais P., Sonigo P. Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses. Nature. 1987 Aug 6;328(6130):543–547. doi: 10.1038/328543a0. [DOI] [PubMed] [Google Scholar]
  5. Charneau P., Mirambeau G., Roux P., Paulous S., Buc H., Clavel F. HIV-1 reverse transcription. A termination step at the center of the genome. J Mol Biol. 1994 Sep 2;241(5):651–662. doi: 10.1006/jmbi.1994.1542. [DOI] [PubMed] [Google Scholar]
  6. Dimitrov D. S., Willey R. L., Martin M. A., Blumenthal R. Kinetics of HIV-1 interactions with sCD4 and CD4+ cells: implications for inhibition of virus infection and initial steps of virus entry into cells. Virology. 1992 Apr;187(2):398–406. doi: 10.1016/0042-6822(92)90441-q. [DOI] [PubMed] [Google Scholar]
  7. Dorfman T., Mammano F., Haseltine W. A., Göttlinger H. G. Role of the matrix protein in the virion association of the human immunodeficiency virus type 1 envelope glycoprotein. J Virol. 1994 Mar;68(3):1689–1696. doi: 10.1128/jvi.68.3.1689-1696.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fan L., Peden K. Cell-free transmission of Vif mutants of HIV-1. Virology. 1992 Sep;190(1):19–29. doi: 10.1016/0042-6822(92)91188-z. [DOI] [PubMed] [Google Scholar]
  9. Fisher A. G., Ensoli B., Ivanoff L., Chamberlain M., Petteway S., Ratner L., Gallo R. C., Wong-Staal F. The sor gene of HIV-1 is required for efficient virus transmission in vitro. Science. 1987 Aug 21;237(4817):888–893. doi: 10.1126/science.3497453. [DOI] [PubMed] [Google Scholar]
  10. Gabuzda D. H., Lawrence K., Langhoff E., Terwilliger E., Dorfman T., Haseltine W. A., Sodroski J. Role of vif in replication of human immunodeficiency virus type 1 in CD4+ T lymphocytes. J Virol. 1992 Nov;66(11):6489–6495. doi: 10.1128/jvi.66.11.6489-6495.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gabuzda D. H., Lever A., Terwilliger E., Sodroski J. Effects of deletions in the cytoplasmic domain on biological functions of human immunodeficiency virus type 1 envelope glycoproteins. J Virol. 1992 Jun;66(6):3306–3315. doi: 10.1128/jvi.66.6.3306-3315.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Garrett E. D., Tiley L. S., Cullen B. R. Rev activates expression of the human immunodeficiency virus type 1 vif and vpr gene products. J Virol. 1991 Mar;65(3):1653–1657. doi: 10.1128/jvi.65.3.1653-1657.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gelderblom H. R., Hausmann E. H., Ozel M., Pauli G., Koch M. A. Fine structure of human immunodeficiency virus (HIV) and immunolocalization of structural proteins. Virology. 1987 Jan;156(1):171–176. doi: 10.1016/0042-6822(87)90449-1. [DOI] [PubMed] [Google Scholar]
  14. Goncalves J., Jallepalli P., Gabuzda D. H. Subcellular localization of the Vif protein of human immunodeficiency virus type 1. J Virol. 1994 Feb;68(2):704–712. doi: 10.1128/jvi.68.2.704-712.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Grewe C., Beck A., Gelderblom H. R. HIV: early virus-cell interactions. J Acquir Immune Defic Syndr. 1990;3(10):965–974. [PubMed] [Google Scholar]
  16. Guy B., Geist M., Dott K., Spehner D., Kieny M. P., Lecocq J. P. A specific inhibitor of cysteine proteases impairs a Vif-dependent modification of human immunodeficiency virus type 1 Env protein. J Virol. 1991 Mar;65(3):1325–1331. doi: 10.1128/jvi.65.3.1325-1331.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Guyader M., Emerman M., Sonigo P., Clavel F., Montagnier L., Alizon M. Genome organization and transactivation of the human immunodeficiency virus type 2. Nature. 1987 Apr 16;326(6114):662–669. doi: 10.1038/326662a0. [DOI] [PubMed] [Google Scholar]
  18. Höglund S., Ohagen A., Lawrence K., Gabuzda D. Role of vif during packing of the core of HIV-1. Virology. 1994 Jun;201(2):349–355. doi: 10.1006/viro.1994.1300. [DOI] [PubMed] [Google Scholar]
  19. Kan N. C., Franchini G., Wong-Staal F., DuBois G. C., Robey W. G., Lautenberger J. A., Papas T. S. Identification of HTLV-III/LAV sor gene product and detection of antibodies in human sera. Science. 1986 Mar 28;231(4745):1553–1555. doi: 10.1126/science.3006245. [DOI] [PubMed] [Google Scholar]
  20. Kim S. Y., Byrn R., Groopman J., Baltimore D. Temporal aspects of DNA and RNA synthesis during human immunodeficiency virus infection: evidence for differential gene expression. J Virol. 1989 Sep;63(9):3708–3713. doi: 10.1128/jvi.63.9.3708-3713.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kishi M., Nishino Y., Sumiya M., Ohki K., Kimura T., Goto T., Nakai M., Kakinuma M., Ikuta K. Cells surviving infection by human immunodeficiency virus type 1: vif or vpu mutants produce non-infectious or markedly less cytopathic viruses. J Gen Virol. 1992 Jan;73(Pt 1):77–87. doi: 10.1099/0022-1317-73-1-77. [DOI] [PubMed] [Google Scholar]
  22. Lusso P., Lori F., Gallo R. C. CD4-independent infection by human immunodeficiency virus type 1 after phenotypic mixing with human T-cell leukemia viruses. J Virol. 1990 Dec;64(12):6341–6344. doi: 10.1128/jvi.64.12.6341-6344.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Oberste M. S., Gonda M. A. Conservation of amino-acid sequence motifs in lentivirus Vif proteins. Virus Genes. 1992 Jan;6(1):95–102. doi: 10.1007/BF01703760. [DOI] [PubMed] [Google Scholar]
  24. Quillent C., Dumey N., Dauguet C., Clavel F. Reversion of a polymerase-defective integrated HIV-1 genome. AIDS Res Hum Retroviruses. 1993 Oct;9(10):1031–1037. doi: 10.1089/aid.1993.9.1031. [DOI] [PubMed] [Google Scholar]
  25. Sakai H., Shibata R., Sakuragi J., Sakuragi S., Kawamura M., Adachi A. Cell-dependent requirement of human immunodeficiency virus type 1 Vif protein for maturation of virus particles. J Virol. 1993 Mar;67(3):1663–1666. doi: 10.1128/jvi.67.3.1663-1666.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Salter R. D., Howell D. N., Cresswell P. Genes regulating HLA class I antigen expression in T-B lymphoblast hybrids. Immunogenetics. 1985;21(3):235–246. doi: 10.1007/BF00375376. [DOI] [PubMed] [Google Scholar]
  27. 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 Aug;183(2):677–686. doi: 10.1016/0042-6822(91)90996-o. [DOI] [PubMed] [Google Scholar]
  28. Sodroski J., Goh W. C., Rosen C., Campbell K., Haseltine W. A. Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity. 1986 Jul 31-Aug 6Nature. 322(6078):470–474. doi: 10.1038/322470a0. [DOI] [PubMed] [Google Scholar]
  29. Sonigo P., Alizon M., Staskus K., Klatzmann D., Cole S., Danos O., Retzel E., Tiollais P., Haase A., Wain-Hobson S. Nucleotide sequence of the visna lentivirus: relationship to the AIDS virus. Cell. 1985 Aug;42(1):369–382. doi: 10.1016/s0092-8674(85)80132-x. [DOI] [PubMed] [Google Scholar]
  30. Sova P., Volsky D. J. Efficiency of viral DNA synthesis during infection of permissive and nonpermissive cells with vif-negative human immunodeficiency virus type 1. J Virol. 1993 Oct;67(10):6322–6326. doi: 10.1128/jvi.67.10.6322-6326.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Spector D. H., Wade E., Wright D. A., Koval V., Clark C., Jaquish D., Spector S. A. Human immunodeficiency virus pseudotypes with expanded cellular and species tropism. J Virol. 1990 May;64(5):2298–2308. doi: 10.1128/jvi.64.5.2298-2308.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Strebel K., Daugherty D., Clouse K., Cohen D., Folks T., Martin M. A. The HIV 'A' (sor) gene product is essential for virus infectivity. Nature. 1987 Aug 20;328(6132):728–730. doi: 10.1038/328728a0. [DOI] [PubMed] [Google Scholar]
  33. Strebel K., Klimkait T., Martin M. A. A novel gene of HIV-1, vpu, and its 16-kilodalton product. Science. 1988 Sep 2;241(4870):1221–1223. doi: 10.1126/science.3261888. [DOI] [PubMed] [Google Scholar]
  34. Sugden B., Marsh K., Yates J. A vector that replicates as a plasmid and can be efficiently selected in B-lymphoblasts transformed by Epstein-Barr virus. Mol Cell Biol. 1985 Feb;5(2):410–413. doi: 10.1128/mcb.5.2.410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M. Nucleotide sequence of the AIDS virus, LAV. Cell. 1985 Jan;40(1):9–17. doi: 10.1016/0092-8674(85)90303-4. [DOI] [PubMed] [Google Scholar]
  36. Willey R. L., Smith D. H., Lasky L. A., Theodore T. S., Earl P. L., Moss B., Capon D. J., Martin M. A. In vitro mutagenesis identifies a region within the envelope gene of the human immunodeficiency virus that is critical for infectivity. J Virol. 1988 Jan;62(1):139–147. doi: 10.1128/jvi.62.1.139-147.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Yu X., Yuan X., Matsuda Z., Lee T. H., Essex M. The matrix protein of human immunodeficiency virus type 1 is required for incorporation of viral envelope protein into mature virions. J Virol. 1992 Aug;66(8):4966–4971. doi: 10.1128/jvi.66.8.4966-4971.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. von Schwedler U., Song J., Aiken C., Trono D. Vif is crucial for human immunodeficiency virus type 1 proviral DNA synthesis in infected cells. J Virol. 1993 Aug;67(8):4945–4955. doi: 10.1128/jvi.67.8.4945-4955.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]

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