Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1993 Nov;67(11):6909–6915. doi: 10.1128/jvi.67.11.6909-6915.1993

Context-dependent role of human immunodeficiency virus type 1 auxiliary genes in the establishment of chronic virus producers.

F Mustafa 1, H L Robinson 1
PMCID: PMC238142  PMID: 8411397

Abstract

Two molecularly cloned viruses, human immunodeficiency virus type 1 (HIV-1)-NL4-3 (NL4-3) and HIV-1-HXB-2 (HXB-2), have been used to study the role of HIV-1 auxiliary genes in the establishment of chronic virus producers. NL4-3 encodes all known HIV-1 proteins, whereas HXB-2 is defective for three auxiliary genes: vpr, vpu, and nef. Studies were done in H9 cells, a T-cell line unusually permissive for the establishment of chronic virus producers. NL4-3 and HXB-2 undergo lytic phases of infection in H9 cultures with HXB-2, but not NL4-3, supporting the efficient establishment of chronic virus producers. Tests of mutant NL4-3 genomes containing various combinations of defective auxiliary genes revealed that both vpr and nef limited the ability of NL4-3 to establish chronic virus producers. Tests of a series of recombinants between NL4-3 and HXB-2 revealed that 5' internal sequences as well as fragments containing defective auxiliary genes affected the establishment of chronic virus producers. Viral envelope sequences and levels of virus production did not correlate with the ability to establish chronic virus producers. These results suggest that complex interactions of viral auxiliary and nonauxiliary gene functions with the host cell determine the ability to establish chronic virus producers.

Full text

PDF
6909

Selected References

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

  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. Anderson S., Shugars D. C., Swanstrom R., Garcia J. V. Nef from primary isolates of human immunodeficiency virus type 1 suppresses surface CD4 expression in human and mouse T cells. J Virol. 1993 Aug;67(8):4923–4931. doi: 10.1128/jvi.67.8.4923-4931.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barré-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vézinet-Brun F., Rouzioux C. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. doi: 10.1126/science.6189183. [DOI] [PubMed] [Google Scholar]
  5. Cheng-Mayer C., Quiroga M., Tung J. W., Dina D., Levy J. A. Viral determinants of human immunodeficiency virus type 1 T-cell or macrophage tropism, cytopathogenicity, and CD4 antigen modulation. J Virol. 1990 Sep;64(9):4390–4398. doi: 10.1128/jvi.64.9.4390-4398.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cheng-Mayer C., Seto D., Levy J. A. Altered host range of HIV-1 after passage through various human cell types. Virology. 1991 Mar;181(1):288–294. doi: 10.1016/0042-6822(91)90494-v. [DOI] [PubMed] [Google Scholar]
  7. Cohen E. A., Dehni G., Sodroski J. G., Haseltine W. A. Human immunodeficiency virus vpr product is a virion-associated regulatory protein. J Virol. 1990 Jun;64(6):3097–3099. doi: 10.1128/jvi.64.6.3097-3099.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cohen E. A., Terwilliger E. F., Jalinoos Y., Proulx J., Sodroski J. G., Haseltine W. A. Identification of HIV-1 vpr product and function. J Acquir Immune Defic Syndr. 1990;3(1):11–18. [PubMed] [Google Scholar]
  9. De Jong J. J., De Ronde A., Keulen W., Tersmette M., Goudsmit J. Minimal requirements for the human immunodeficiency virus type 1 V3 domain to support the syncytium-inducing phenotype: analysis by single amino acid substitution. J Virol. 1992 Nov;66(11):6777–6780. doi: 10.1128/jvi.66.11.6777-6780.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Evans L. A., McHugh T. M., Stites D. P., Levy J. A. Differential ability of human immunodeficiency virus isolates to productively infect human cells. J Immunol. 1987 May 15;138(10):3415–3418. [PubMed] [Google Scholar]
  11. Fernandez-Larsson R., Srivastava K. K., Lu S., Robinson H. L. Replication of patient isolates of human immunodeficiency virus type 1 in T cells: a spectrum of rates and efficiencies of entry. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2223–2226. doi: 10.1073/pnas.89.6.2223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fisher A. G., Collalti E., Ratner L., Gallo R. C., Wong-Staal F. A molecular clone of HTLV-III with biological activity. Nature. 1985 Jul 18;316(6025):262–265. doi: 10.1038/316262a0. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Garcia J. V., Alfano J., Miller A. D. The negative effect of human immunodeficiency virus type 1 Nef on cell surface CD4 expression is not species specific and requires the cytoplasmic domain of CD4. J Virol. 1993 Mar;67(3):1511–1516. doi: 10.1128/jvi.67.3.1511-1516.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Garcia J. V., Miller A. D. Serine phosphorylation-independent downregulation of cell-surface CD4 by nef. Nature. 1991 Apr 11;350(6318):508–511. doi: 10.1038/350508a0. [DOI] [PubMed] [Google Scholar]
  16. Guy B., Kieny M. P., Riviere Y., Le Peuch C., Dott K., Girard M., Montagnier L., Lecocq J. P. HIV F/3' orf encodes a phosphorylated GTP-binding protein resembling an oncogene product. Nature. 1987 Nov 19;330(6145):266–269. doi: 10.1038/330266a0. [DOI] [PubMed] [Google Scholar]
  17. 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 U S A. 1990 Oct;87(20):8080–8084. doi: 10.1073/pnas.87.20.8080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hirsch I., Salaun D., Brichacek B., Chermann J. C. HIV1 cytopathogenicity-genetic difference between direct cytotoxic and fusogenic effect. Virology. 1992 Feb;186(2):647–654. doi: 10.1016/0042-6822(92)90031-j. [DOI] [PubMed] [Google Scholar]
  19. Hovanessian A. G. On the HIV nef gene product. Res Virol. 1992 Jan-Feb;143(1):31–34. doi: 10.1016/s0923-2516(06)80074-9. [DOI] [PubMed] [Google Scholar]
  20. Hoxie J. A., Brass L. F., Pletcher C. H., Haggarty B. S., Hahn B. H. Cytopathic variants of an attenuated isolate of human immunodeficiency virus type 2 exhibit increased affinity for CD4. J Virol. 1991 Sep;65(9):5096–5101. doi: 10.1128/jvi.65.9.5096-5101.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Koga Y., Sasaki M., Nakamura K., Kimura G., Nomoto K. Intracellular distribution of the envelope glycoprotein of human immunodeficiency virus and its role in the production of cytopathic effect in CD4+ and CD4- human cell lines. J Virol. 1990 Oct;64(10):4661–4671. doi: 10.1128/jvi.64.10.4661-4671.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kowalski M., Bergeron L., Dorfman T., Haseltine W., Sodroski J. Attenuation of human immunodeficiency virus type 1 cytopathic effect by a mutation affecting the transmembrane envelope glycoprotein. J Virol. 1991 Jan;65(1):281–291. doi: 10.1128/jvi.65.1.281-291.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lang S. M., Weeger M., Stahl-Hennig C., Coulibaly C., Hunsmann G., Müller J., Müller-Hermelink H., Fuchs D., Wachter H., Daniel M. M. Importance of vpr for infection of rhesus monkeys with simian immunodeficiency virus. J Virol. 1993 Feb;67(2):902–912. doi: 10.1128/jvi.67.2.902-912.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Leonard R., Zagury D., Desportes I., Bernard J., Zagury J. F., Gallo R. C. Cytopathic effect of human immunodeficiency virus in T4 cells is linked to the last stage of virus infection. Proc Natl Acad Sci U S A. 1988 May;85(10):3570–3574. doi: 10.1073/pnas.85.10.3570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Luria S., Chambers I., Berg P. Expression of the type 1 human immunodeficiency virus Nef protein in T cells prevents antigen receptor-mediated induction of interleukin 2 mRNA. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5326–5330. doi: 10.1073/pnas.88.12.5326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Niederman T. M., Garcia J. V., Hastings W. R., Luria S., Ratner L. Human immunodeficiency virus type 1 Nef protein inhibits NF-kappa B induction in human T cells. J Virol. 1992 Oct;66(10):6213–6219. doi: 10.1128/jvi.66.10.6213-6219.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Niederman T. M., Hastings W. R., Luria S., Bandres J. C., Ratner L. HIV-1 Nef protein inhibits the recruitment of AP-1 DNA-binding activity in human T-cells. Virology. 1993 May;194(1):338–344. doi: 10.1006/viro.1993.1264. [DOI] [PubMed] [Google Scholar]
  28. Popovic M., Sarngadharan M. G., Read E., Gallo R. C. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. doi: 10.1126/science.6200935. [DOI] [PubMed] [Google Scholar]
  29. Robinson H. L., Zinkus D. M. Accumulation of human immunodeficiency virus type 1 DNA in T cells: results of multiple infection events. J Virol. 1990 Oct;64(10):4836–4841. doi: 10.1128/jvi.64.10.4836-4841.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sakai K., Dewhurst S., Ma X. Y., Volsky D. J. Differences in cytopathogenicity and host cell range among infectious molecular clones of human immunodeficiency virus type 1 simultaneously isolated from an individual. J Virol. 1988 Nov;62(11):4078–4085. doi: 10.1128/jvi.62.11.4078-4085.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sakai K., Ma X. Y., Gordienko I., Volsky D. J. Recombinational analysis of a natural noncytopathic human immunodeficiency virus type 1 (HIV-1) isolate: role of the vif gene in HIV-1 infection kinetics and cytopathicity. J Virol. 1991 Nov;65(11):5765–5773. doi: 10.1128/jvi.65.11.5765-5773.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Skowronski J., Parks D., Mariani R. Altered T cell activation and development in transgenic mice expressing the HIV-1 nef gene. EMBO J. 1993 Feb;12(2):703–713. doi: 10.1002/j.1460-2075.1993.tb05704.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Somasundaran M., Robinson H. L. A major mechanism of human immunodeficiency virus-induced cell killing does not involve cell fusion. J Virol. 1987 Oct;61(10):3114–3119. doi: 10.1128/jvi.61.10.3114-3119.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Somasundaran M., Robinson H. L. Unexpectedly high levels of HIV-1 RNA and protein synthesis in a cytocidal infection. Science. 1988 Dec 16;242(4885):1554–1557. doi: 10.1126/science.3201245. [DOI] [PubMed] [Google Scholar]
  36. Spire B., Hirsch I., Neuveut C., Sire J., Chermann J. C. The env gene variability is not directly related to the high cytopathogenicity of an HIV1 variant. Virology. 1990 Aug;177(2):756–758. doi: 10.1016/0042-6822(90)90543-z. [DOI] [PubMed] [Google Scholar]
  37. Stevenson M., Haggerty S., Lamonica C., Mann A. M., Meier C., Wasiak A. Cloning and characterization of human immunodeficiency virus type 1 variants diminished in the ability to induce syncytium-independent cytolysis. J Virol. 1990 Aug;64(8):3792–3803. doi: 10.1128/jvi.64.8.3792-3803.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. 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]
  39. Wain-Hobson S., Vartanian J. P., Henry M., Chenciner N., Cheynier R., Delassus S., Martins L. P., Sala M., Nugeyre M. T., Guétard D. LAV revisited: origins of the early HIV-1 isolates from Institut Pasteur. Science. 1991 May 17;252(5008):961–965. doi: 10.1126/science.2035026. [DOI] [PubMed] [Google Scholar]
  40. Wildavsky A., Todhunter J. A., Havender W. R. Formaldehyde regulation. Science. 1984 May 11;224(4649):550,552,554-6. doi: 10.1126/science.6710155. [DOI] [PubMed] [Google Scholar]
  41. York-Higgins D., Cheng-Mayer C., Bauer D., Levy J. A., Dina D. Human immunodeficiency virus type 1 cellular host range, replication, and cytopathicity are linked to the envelope region of the viral genome. J Virol. 1990 Aug;64(8):4016–4020. doi: 10.1128/jvi.64.8.4016-4020.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES