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. 1991 Nov;65(11):5765–5773. doi: 10.1128/jvi.65.11.5765-5773.1991

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.

K Sakai 1, X Y Ma 1, I Gordienko 1, D J Volsky 1
PMCID: PMC250237  PMID: 1920615

Abstract

Two molecularly cloned coisolates of human immunodeficiency virus type 1 (HIV-1) have been found to exhibit different phenotypes of viral expression, either rapid and cytopathic (N1T-A virus) or delayed and noncytopathic (N1T-E virus [X. Ma, K. Sakai, F. Sinangil, E. Golub, and D. J. Volsky, Virology 176:184-194, 1990]). To identify the viral genetic elements responsible for these phenotypes, we prepared reciprocal recombinants in different regions of N1T-A and N1T-E viral genomes. Infectivity experiments with the recombinant viruses revealed that the rapid/cytopathic (N1T-A-like) phenotype assorted cleanly with the V1f-coding region and Vif expression. The smallest HIV-1 DNA region that conferred the complete phenotypic switch was a 284-bp NdeI-StuI fragment within the vif open reading frame. Nucleotide sequence analysis revealed a 35-bp deletion starting at nucleotide 218 in the N1T-E vif gene. A 23-kDa Vif protein was detected by immunoblotting using Vif-specific antiserum in extracts of cells infected with N1T-A but not N1T-E virus. No detectable vif protein was found in association with sedimented particles of either virus. Cotransfection of a eucaryotic vif expression plasmid with N1T-E DNA complemented the N1T-E defect; rapid/cytopathic infection similar to that in N1T-A-transfected cells was observed. We conclude that Vif controls the rate, and consequently the cytopathic outcome, of HIV-1 infection.

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Selected References

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  1. Asjö B., Morfeldt-Månson L., Albert J., Biberfeld G., Karlsson A., Lidman K., Fenyö E. M. Replicative capacity of human immunodeficiency virus from patients with varying severity of HIV infection. Lancet. 1986 Sep 20;2(8508):660–662. [PubMed] [Google Scholar]
  2. Casareale D., Dewhurst S., Sonnabend J., Sinangil F., Purtilo D. T., Volsky D. J. Prevalence of AIDS-associated retrovirus and antibodies among male homosexuals at risk for AIDS in Greenwich Village. AIDS Res. 1984;1(6):407–421. doi: 10.1089/aid.1.1983.1.407. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Citovsky V., Knorr D., Schuster G., Zambryski P. The P30 movement protein of tobacco mosaic virus is a single-strand nucleic acid binding protein. Cell. 1990 Feb 23;60(4):637–647. doi: 10.1016/0092-8674(90)90667-4. [DOI] [PubMed] [Google Scholar]
  5. Concar D., Anderson C. Assumptions of AIDS inquiry challenged. Nature. 1990 Sep 6;347(6288):3–3. doi: 10.1038/347003a0. [DOI] [PubMed] [Google Scholar]
  6. Evans L. A., Levy J. A. Characteristics of HIV infection and pathogenesis. Biochim Biophys Acta. 1989 Dec 27;989(3):237–254. [PubMed] [Google Scholar]
  7. 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]
  8. Evans L. A., Moreau J., Odehouri K., Legg H., Barboza A., Cheng-Mayer C., Levy J. A. Characterization of a noncytopathic HIV-2 strain with unusual effects on CD4 expression. Science. 1988 Jun 10;240(4858):1522–1525. doi: 10.1126/science.2836951. [DOI] [PubMed] [Google Scholar]
  9. FOLEY G. E., LAZARUS H., FARBER S., UZMAN B. G., BOONE B. A., MCCARTHY R. E. CONTINUOUS CULTURE OF HUMAN LYMPHOBLASTS FROM PERIPHERAL BLOOD OF A CHILD WITH ACUTE LEUKEMIA. Cancer. 1965 Apr;18:522–529. doi: 10.1002/1097-0142(196504)18:4<522::aid-cncr2820180418>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  10. Fenyö E. M., Morfeldt-Månson L., Chiodi F., Lind B., von Gegerfelt A., Albert J., Olausson E., Asjö B. Distinct replicative and cytopathic characteristics of human immunodeficiency virus isolates. J Virol. 1988 Nov;62(11):4414–4419. doi: 10.1128/jvi.62.11.4414-4419.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Fisher A. G., Ensoli B., Looney D., Rose A., Gallo R. C., Saag M. S., Shaw G. M., Hahn B. H., Wong-Staal F. Biologically diverse molecular variants within a single HIV-1 isolate. Nature. 1988 Aug 4;334(6181):444–447. doi: 10.1038/334444a0. [DOI] [PubMed] [Google Scholar]
  13. Fisher A. G., Ratner L., Mitsuya H., Marselle L. M., Harper M. E., Broder S., Gallo R. C., Wong-Staal F. Infectious mutants of HTLV-III with changes in the 3' region and markedly reduced cytopathic effects. Science. 1986 Aug 8;233(4764):655–659. doi: 10.1126/science.3014663. [DOI] [PubMed] [Google Scholar]
  14. Gallo R. C., Salahuddin S. Z., Popovic M., Shearer G. M., Kaplan M., Haynes B. F., Palker T. J., Redfield R., Oleske J., Safai B. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984 May 4;224(4648):500–503. doi: 10.1126/science.6200936. [DOI] [PubMed] [Google Scholar]
  15. Gazdar A. F., Carney D. N., Bunn P. A., Russell E. K., Jaffe E. S., Schechter G. P., Guccion J. G. Mitogen requirements for the in vitro propagation of cutaneous T-cell lymphomas. Blood. 1980 Mar;55(3):409–417. [PubMed] [Google Scholar]
  16. Golub E. I., Li G. G., Volsky D. J. Differences in the basal activity of the long terminal repeat determine different replicative capacities of two closely related human immunodeficiency virus type 1 isolates. J Virol. 1990 Aug;64(8):3654–3660. doi: 10.1128/jvi.64.8.3654-3660.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Hahn B. H., Gonda M. A., Shaw G. M., Popovic M., Hoxie J. A., Gallo R. C., Wong-Staal F. Genomic diversity of the acquired immune deficiency syndrome virus HTLV-III: different viruses exhibit greatest divergence in their envelope genes. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4813–4817. doi: 10.1073/pnas.82.14.4813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Haseltine W. A. Replication and pathogenesis of the AIDS virus. J Acquir Immune Defic Syndr. 1988;1(3):217–240. [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. Klatzmann D., Barré-Sinoussi F., Nugeyre M. T., Danquet C., Vilmer E., Griscelli C., Brun-Veziret F., Rouzioux C., Gluckman J. C., Chermann J. C. Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes. Science. 1984 Jul 6;225(4657):59–63. doi: 10.1126/science.6328660. [DOI] [PubMed] [Google Scholar]
  22. Kong L. I., Lee S. W., Kappes J. C., Parkin J. S., Decker D., Hoxie J. A., Hahn B. H., Shaw G. M. West African HIV-2-related human retrovirus with attenuated cytopathicity. Science. 1988 Jun 10;240(4858):1525–1529. doi: 10.1126/science.3375832. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Lifson J. D., Reyes G. R., McGrath M. S., Stein B. S., Engleman E. G. AIDS retrovirus induced cytopathology: giant cell formation and involvement of CD4 antigen. Science. 1986 May 30;232(4754):1123–1127. doi: 10.1126/science.3010463. [DOI] [PubMed] [Google Scholar]
  25. Looney D. J., Fisher A. G., Putney S. D., Rusche J. R., Redfield R. R., Burke D. S., Gallo R. C., Wong-Staal F. Type-restricted neutralization of molecular clones of human immunodeficiency virus. Science. 1988 Jul 15;241(4863):357–359. doi: 10.1126/science.3388046. [DOI] [PubMed] [Google Scholar]
  26. Ma X. Y., Sakai K., Sinangil F., Golub E., Volsky D. J. Interaction of a noncytopathic human immunodeficiency virus type 1 (HIV-1) with target cells: efficient virus entry followed by delayed expression of its RNA and protein. Virology. 1990 May;176(1):184–194. doi: 10.1016/0042-6822(90)90243-k. [DOI] [PubMed] [Google Scholar]
  27. Poli G., Kinter A., Justement J. S., Kehrl J. H., Bressler P., Stanley S., Fauci A. S. Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression. Proc Natl Acad Sci U S A. 1990 Jan;87(2):782–785. doi: 10.1073/pnas.87.2.782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Robert-Guroff M., Reitz M. S., Jr, Robey W. G., Gallo R. C. In vitro generation of an HTLV-III variant by neutralizing antibody. J Immunol. 1986 Nov 15;137(10):3306–3309. [PubMed] [Google Scholar]
  29. 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]
  30. Sakai K., Ma X. Y., Volsky D. J. Low-cytopathic infectious clone of human immunodeficiency virus type I (HIV-I). FEBS Lett. 1988 Oct 10;238(2):257–261. doi: 10.1016/0014-5793(88)80491-5. [DOI] [PubMed] [Google Scholar]
  31. Shaw G. M., Hahn B. H., Arya S. K., Groopman J. E., Gallo R. C., Wong-Staal F. Molecular characterization of human T-cell leukemia (lymphotropic) virus type III in the acquired immune deficiency syndrome. Science. 1984 Dec 7;226(4679):1165–1171. doi: 10.1126/science.6095449. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Sodroski J., Goh W. C., Rosen C., Tartar A., Portetelle D., Burny A., Haseltine W. Replicative and cytopathic potential of HTLV-III/LAV with sor gene deletions. Science. 1986 Mar 28;231(4745):1549–1553. doi: 10.1126/science.3006244. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Stein B. S., Gowda S. D., Lifson J. D., Penhallow R. C., Bensch K. G., Engleman E. G. pH-independent HIV entry into CD4-positive T cells via virus envelope fusion to the plasma membrane. Cell. 1987 Jun 5;49(5):659–668. doi: 10.1016/0092-8674(87)90542-3. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. 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]
  38. Tersmette M., de Goede R. E., Al B. J., Winkel I. N., Gruters R. A., Cuypers H. T., Huisman H. G., Miedema F. Differential syncytium-inducing capacity of human immunodeficiency virus isolates: frequent detection of syncytium-inducing isolates in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. J Virol. 1988 Jun;62(6):2026–2032. doi: 10.1128/jvi.62.6.2026-2032.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Volsky D. J., Sakai K., Stevenson M., Dewhurst S. Retroviral etiology of the acquired immune deficiency syndrome (AIDS). AIDS Res. 1986 Dec;2 (Suppl 1):S35–S48. [PubMed] [Google Scholar]
  40. Wong-Staal F., Shaw G. M., Hahn B. H., Salahuddin S. Z., Popovic M., Markham P., Redfield R., Gallo R. C. Genomic diversity of human T-lymphotropic virus type III (HTLV-III). Science. 1985 Aug 23;229(4715):759–762. doi: 10.1126/science.2992084. [DOI] [PubMed] [Google Scholar]
  41. von Briesen H., Becker W. B., Henco K., Helm E. B., Gelderblom H. R., Brede H. D., Rübsamen-Waigmann H. Isolation frequency and growth properties of HIV-variants: multiple simultaneous variants in a patient demonstrated by molecular cloning. J Med Virol. 1987 Sep;23(1):51–66. doi: 10.1002/jmv.1890230107. [DOI] [PubMed] [Google Scholar]

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