Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1997 Mar;71(3):2473–2477. doi: 10.1128/jvi.71.3.2473-2477.1997

Phenotypically Vif- human immunodeficiency virus type 1 is produced by chronically infected restrictive cells.

M Bouyac 1, F Rey 1, M Nascimbeni 1, M Courcoul 1, J Sire 1, D Blanc 1, F Clavel 1, R Vigne 1, B Spire 1
PMCID: PMC191358  PMID: 9032385

Abstract

The permissivity of CD4+ transformed T cells for the replication of human immunodeficiency virus type 1 (HIV-1) vif mutants varies widely between different cell lines. Mutant vif-negative viruses propagate normally in permissive CD4+ cell lines but are unable to establish a productive infection in restrictive cell lines such as H9. As a consequence, elucidation of the function of Vif has been considerably hampered by the inherent difficulty in obtaining a stable source of authentically replication-defective vif-negative viral particles produced by restrictive cells. vif-negative, vpr-negative HIV-1 strain NDK stock, produced by the permissive SupT1 cell line, was used to infect restrictive H9 cells. By using a high multiplicity, infection of H9 cells was achieved, leading to persistent production of viral particles displaying a dramatically reduced infectious virus titer when measured in a single-cycle infectivity assay. Although these viral particles were unable to further propagate in H9 cells, they could replicate normally in CEM and SupT1 cells. Comparison of unprocessed and processed Gag proteins in the persistently produced vif-negative viral particles revealed no defect in the processing of polypeptide precursors, with no inversion of the Pr55gag/p24 ratio. In addition, there was no defect in Env incorporation for the vif-negative viral particles. Despite their apparently normal protein content, these particles were morphologically abnormal when examined by transmission electron microscopy, displaying a previously described abnormally condensed nucleoid. Chronically infected restrictive cell lines producing stable levels of phenotypically vif-negative HIV-1 particles could prove particularly useful in further studies on the function of Vif in the virus life cycle.

Full Text

The Full Text of this article is available as a PDF (394.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. 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]
  2. Borman A. M., Quillent C., Charneau P., Dauguet C., Clavel F. Human immunodeficiency virus type 1 Vif- mutant particles from restrictive cells: role of Vif in correct particle assembly and infectivity. J Virol. 1995 Apr;69(4):2058–2067. doi: 10.1128/jvi.69.4.2058-2067.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Courcoul M., Patience C., Rey F., Blanc D., Harmache A., Sire J., Vigne R., Spire B. Peripheral blood mononuclear cells produce normal amounts of defective Vif- human immunodeficiency virus type 1 particles which are restricted for the preretrotranscription steps. J Virol. 1995 Apr;69(4):2068–2074. doi: 10.1128/jvi.69.4.2068-2074.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Desrosiers R. C. HIV with multiple gene deletions as a live attenuated vaccine for AIDS. AIDS Res Hum Retroviruses. 1992 Mar;8(3):411–421. doi: 10.1089/aid.1992.8.411. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. 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]
  9. Harmache A., Russo P., Vitu C., Guiguen F., Mornex J. F., Pepin M., Vigne R., Suzan M. Replication in goats in vivo of caprine arthritis-encephalitis virus deleted in vif or tat genes: possible use of these deletion mutants as live vaccines. AIDS Res Hum Retroviruses. 1996 Mar 20;12(5):409–411. doi: 10.1089/aid.1996.12.409. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Liu H., Wu X., Newman M., Shaw G. M., Hahn B. H., Kappes J. C. The Vif protein of human and simian immunodeficiency viruses is packaged into virions and associates with viral core structures. J Virol. 1995 Dec;69(12):7630–7638. doi: 10.1128/jvi.69.12.7630-7638.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Rey F., Donker G., Hirsch I., Chermann J. C. Productive infection of CD4+ cells by selected HIV strains is not inhibited by anti-CD4 monoclonal antibodies. Virology. 1991 Mar;181(1):165–171. doi: 10.1016/0042-6822(91)90481-p. [DOI] [PubMed] [Google Scholar]
  13. Rey M. A., Spire B., Dormont D., Barre-Sinoussi F., Montagnier L., Chermann J. C. Characterization of the RNA dependent DNA polymerase of a new human T-lymphotropic retrovirus (lymphadenopathy associated virus). Biochem Biophys Res Commun. 1984 May 31;121(1):126–133. doi: 10.1016/0006-291x(84)90696-x. [DOI] [PubMed] [Google Scholar]
  14. Rogel M. E., Wu L. I., Emerman M. The human immunodeficiency virus type 1 vpr gene prevents cell proliferation during chronic infection. J Virol. 1995 Feb;69(2):882–888. doi: 10.1128/jvi.69.2.882-888.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Simm M., Shahabuddin M., Chao W., Allan J. S., Volsky D. J. Aberrant Gag protein composition of a human immunodeficiency virus type 1 vif mutant produced in primary lymphocytes. J Virol. 1995 Jul;69(7):4582–4586. doi: 10.1128/jvi.69.7.4582-4586.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Simon J. H., Malim M. H. The human immunodeficiency virus type 1 Vif protein modulates the postpenetration stability of viral nucleoprotein complexes. J Virol. 1996 Aug;70(8):5297–5305. doi: 10.1128/jvi.70.8.5297-5305.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Spire B., Sire J., Zachar V., Rey F., Barré-Sinoussi F., Galibert F., Hampe A., Chermann J. C. Nucleotide sequence of HIV1-NDK: a highly cytopathic strain of the human immunodeficiency virus. Gene. 1989 Sep 30;81(2):275–284. doi: 10.1016/0378-1119(89)90188-1. [DOI] [PubMed] [Google Scholar]
  20. Trono D. HIV accessory proteins: leading roles for the supporting cast. Cell. 1995 Jul 28;82(2):189–192. doi: 10.1016/0092-8674(95)90306-2. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. 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]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES