1887

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Volume 74, Issue 12

The cytopathic effect of human immunodeficiency virus is independent of high levels of unintegrated viral DNA accumulated in response to superinfection of cells Free

Abstract

Large quantities of genome-sized viral DNA are detected in the nucleoplasm of CD4 T cells infected with human immunodeficiency virus type 1 (HIV-1). This unintegrated HIV DNA is in the form of both circular and linear species. Accumulation of such DNA occurs gradually during a 5 day HIV infection and is correlated with the proportion of cells involved in the production of HIV proteins. To pinpoint the stage in a synchronized HIV infection during which accumulation of HIV DNA occurs, high titres of HIV were employed to infect CEM cells to infect the majority of cells by the input virus. By this latter infection, more than 95% of cells became producers of HIV proteins at 48 h post-infection (p.i.) concomitantly with the development of the c.p.e. of HIV, manifested by formation of syncytia and induction of cell death by apoptosis. Addition of azidothymidine (AZT) or neutralizing anti-gp 120 monoclonal antibodies at 8 h p.i. did not alter the course of virus infection nor the amount of virus produced at 48 h p.i. but the accumulation of unintegrated HIV DNA was drastically reduced. These results indicate that viral DNA accumulates as a result of superinfection of cells late in the virus cycle. The development of the c.p.e. of HIV was inhibited in the presence of neutralizing antibodies, whereas in the presence of AZT the accumulation of unintegrated HIV DNA was completely blocked without apparent effect on the c.p.e. These observations indicate that the c.p.e. of the HIV infection, which is manifested by syncytium formation and apoptosis, does not require superinfection of cells or accumulation of unintegrated viral DNA.

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© Journal of General Virology 1993
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1993-12-01
2024-04-25
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References

  1. Agy M. B., Wambach M., Foy K., Katzk M. G. 1990; Expression of cellular genes in CD4 positive lymphoid cells infected by the human immunodeficiency virus, HIV-1: evidence for a host protein synthesis shut-off induced by cellular mRNA degradation. Virology 177:251–258
     [Google Scholar]
  2. Ameisen J. C. 1992; Programmed cell death and AIDS: from hypothesis to experiment. Immunology Today 13:388–391
     [Google Scholar]
  3. Ameisen J. C., Capron A. 1991; Cell dysfunction and depletion in AIDS: the programmed cell death hypothesis. Immunology Today 12:102–105
     [Google Scholar]
  4. Bagasra O., Hauptman S. P., Harold D. O., Lischner W., Sachs M., Pomerantz R. J. 1992; Detection of human immunodeficiency virus type 1 provirus in mononuclear cells by in situ polymerase chain reaction. New England Journal of Medicine 326:1385–1391
     [Google Scholar]
  5. Bergeron L., Sodroski J. 1992; Dissociation of unintegrated viral DNA accumulation from single cell lysis induced by human immunodeficiency virus type 1. Journal of Virology 66:5777–5787
     [Google Scholar]
  6. Besansky N. J., Butera S. T., Sinha S., Folks T. M. 1991; Unintegrated human immunodeficiency virus type 1 DNA in chronically infected cell lines is not correlated with surface CD4 expression. Journal of Virology 65:2695–2698
     [Google Scholar]
  7. Bukrinsky M. I., Stanwick T. L., Dempsey M. P., Stevenson M. 1991; Quiescent T lymphocytes as an inducible virus reservoir in HIV-1 infection. Science 254:423–427
     [Google Scholar]
  8. Charneau P., Clavel F. 1991; A single-stranded gap in human immunodeficiency virus unintegrated linear DNA defined by a central copy of the polypurine tract. Journal of Virology 65:2415–2421
     [Google Scholar]
  9. Cheng-Mayer C., Seto D., Tateno D., Levy J. A. 1988; Biologic features of HIV-1 that correlate with virulence in the host. Science 240:80–82
     [Google Scholar]
  10. Cullen B. R. 1991; Regulation of human immunodeficiency virus replication. Annual Review of Microbiology 45:19–50
     [Google Scholar]
  11. Dickover R. E., Donovan R. M., Goldstein E., Cohen S. H., Bolton V., Huth R. G., Liu G., Carlson J. R. 1992; Decreases in unintegrated HIV DNA are associated with antiretroviral therapy in AIDS patients. Journal of AIDS 5:31–36
     [Google Scholar]
  12. Duvall E., Wyllie A. H. 1986; Death and the cell. Immunology Today 1:115–119
     [Google Scholar]
  13. Fenyö E. M., Morfeldt-Manson L., Chiodi F., Lind B., Von Gegerfelt A., Albert J., Albert E., Olausson E., Asjö B. 1988; Distinct replicative and cytopathic characteristics of human immunodeficiency virus isolates. Journal of Virology 62:4414–4419
     [Google Scholar]
  14. Grandgenett D. P., Mumm S. R. 1990; Unraveling retrovirus integration. Cell 60:3–4
     [Google Scholar]
  15. Haase A. T. 1986; Pathogenesis of lentivirus infections. Nature, London 322:130–136
     [Google Scholar]
  16. Hirsch V. M., Zack P. M., Vogel A. P., Johnson P. R. 1991; Simian immunodeficiency virus infection of macaques: end-stage disease is characterized by widespread distribution of proviral DNA in tissues. Journal of AIDS 163:976–988
     [Google Scholar]
  17. Hsia K., Spector S. A. 1991; Human immunodeficiency virus DNA is present in a high percentage of CD4+ lymphocytes of seropositive individuals. Journal of AIDS 164:470–475
     [Google Scholar]
  18. Keshet E., Temin H. 1979; Cell killing by spleen necrosis virus is correlated with a transient accumulation of spleen necrosis virus DNA. Journal of Virology 31:376–388
     [Google Scholar]
  19. Kim S., Byrn R., Groopman J., Baltimore D. 1989; Temporal aspects of DNA and RNA synthesis during human immunodeficiency virus infection: evidence for differential gene expression. Journal of Virology 63:3708–3713
     [Google Scholar]
  20. Kinney-Thomas E., Weber J. N., McClure J., Clapham P. R., Singhal M. C., Shriver M. K., Weiss R. 1988; Neutralising monoclonal antibodies to the AIDS virus. AIDS 2:25–29
     [Google Scholar]
  21. Krust B., Callebaut C., Hovanessian A. G. 1993; Inhibition of entry of HIV particles in cells by poly(A).poly(U). AIDS Research and Human Retroviruses (in press)
    [Google Scholar]
  22. Laurent A. G., Krust B., Rey M. A., Montagnier L., Hovanessian A. G. 1989; Cell surface expression of several species of human immunodeficiency virus type 1 major core protein. Journal of Virology 63:4074–4078
     [Google Scholar]
  23. Laurent A. G., Hovanessian A. G., Rivière Y., Krust B., Regnault A., Montagnier L., Findeli A., Kieny M. P., Guy B. 1990; Production of a non-functional nef protein in human immunodeficiency virus type 1-infected CEM cells. Journal of General Virology 71:2273–2281
     [Google Scholar]
  24. Laurent-Crawford A. G., Krust B., Muller S., Rivière Y., Rey-Cuille M. A., Bechet J. M., Montagnier L., Hovanessian A. G. 1991; The cytopathic effect of HIV is associated with apoptosis. Virology 185:829–839
     [Google Scholar]
  25. Laurent-Crawford A. G., Krust B., Deschamps de Paillette E., Montagnier L., Hovanessian A. G. 1992a; Antiviral action of polyadenylic-polyuridylic acid against HIV in cell cultures. AIDS Research and Human Retroviruses 8:285–290
     [Google Scholar]
  26. Laurent-Crawford A. G., Krust B., Rey M. A., Cointe D., Coccia E., Riviere Y., Muller S., Kieny M. P., Dauguet C., Hovanessian A. G. 1992b; Membrane expression of HIV envelope glycoproteins triggers apoptosis in CD4 cells: a direct mechanism for T4 cells depletion mediated by virus replication. In Retroviruses of Human AIDS and Related Animal Diseases pp 35–11 Edited by Girard M., Valette L. France: Pasteur Merieux;
     [Google Scholar]
  27. Laurent-Crawford A. G., Krust B., Rivière Y., Desgranges C., Muller S., Kieny M. P., Dauguet C., Hovanessian A. G. 1993; Membrane expression of HIV envelope glycoproteins triggers apoptosis in CD4 cells. AIDS Research and Human Retroviruses 9:761–773
     [Google Scholar]
  28. Lifson J. D., Feinberg M. B., Reyes G. R., Rabin L., Bonapour A., Chakrabarti S., Moss B., Wong-Staal F., Steimer K. S., Engleman E. G. 1986; Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein. Nature, London 323:725–728
     [Google Scholar]
  29. Linsley P. S., Ledbetter J. A., Kinney-Thomas E., Hu S. L. 1988; Effects of anti-gpl20 monoclonal antibodies on CD4 receptor binding by the env protein of human immunodeficiency virus type 1. Journal of Virology 62:3695–3702
     [Google Scholar]
  30. Marsh M., Dalgleish A. 1988; How do human immunodeficiency viruses enter cells?. Immunology Today 8:369–371
     [Google Scholar]
  31. Mergia A., Luciw P. A. 1991; Replication and regulation of primate foamy viruses. Virology 184:475–482
     [Google Scholar]
  32. Muesing M. A., Smith D. H., Cabradilla C. D., Benton C. V., Lasky L. A., Capon D. J. 1985; Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus. Nature, London 313:450–458
     [Google Scholar]
  33. Mullins J. I., Chen C. S., Hoover E. A. 1986; Disease-specific and tissue-specific production of unintegrated feline leukemia virus variant DNA in feline AIDS. Nature, London 319:333–336
     [Google Scholar]
  34. Pang S., Koyanagi Y., Miles S., Wiley C., Vinters H. V., Chen I. S. Y. 1990; High levels of unintegrated HIV-1 DNA in brain tissue of AIDS dementia patients. Nature, London 343:85–89
     [Google Scholar]
  35. Pauza C. D., Galindo J. E. 1989; Persistent human immunodeficiency virus type 1 infection of monoblastoid cells leads to accumulation of self-integrated viral DNA and to production of defective virions. Journal of Virology 63:3700–3707
     [Google Scholar]
  36. Pauza C. D., Singh M. K. 1990; Extrachromosomal HIV-1 DNA in persistently infected U 937 cells. AIDS Research and Human Retroviruses 6:1027–1030
     [Google Scholar]
  37. Pauza C. D., Galindo J. E., Richman D. D. 1990; Reinfection results in accumulation of unintegrated viral DNA in cytopathic and persistent human immunodeficiency virus type 1 infection of CEM cells. Journal of Experimental Medicine 172:1035–1042
     [Google Scholar]
  38. Rey M. A., Krust B., Laurent A. G., Montagnier L., Hovanessian A. G. 1989a; Characterization of HIV-2 envelope glycoproteins: dimerization of the glycoprotein precursor during its processing. Journal of Virology 63:647–658
     [Google Scholar]
  39. Rey M. A., Krust B., Laurent A. G., Guetard D., Montagnier L., Hovanessian A. G. 1989b; Characterization of an HIV-2 related virus with a smaller sized extracellular envelope glycoprotein. Virology 173:258–267
     [Google Scholar]
  40. Robinson H. L., Zinkus D. M. 1990; Accumulation of human immunodeficiency virus type 1 DNA in T cells: result of multiple infection events. Journal of Virology 64:4836–4851
     [Google Scholar]
  41. Rosenberg Z. F., Fauci A. S. 1991; Immunopathogenesis of HIV infection. FASEB Journal 5:2382–2390
     [Google Scholar]
  42. Schellekens P. TH. A., Tersmette M., Roos M. T. L., Keet R. P., de Wolf F., Coutinho R. A., Miedema F. 1992; Biphasic rate of CD4+ cell count decline during progression to AIDS correlates with HIV-1 phenotype. AIDS 6:665–669
     [Google Scholar]
  43. Schnittmann S. M., Greenhouse J. J., Psallidopoulos M. C., Baseler M., Salzman N. P., Fauci A. S., Lane H. C. 1990; Increasing viral burden in CD4+ T cells in patients with human immunodeficiency virus (HIV) infection reflects rapidly progressive immunosuppression and clinical disease. Annals of Internal Medicine 113:438–143
     [Google Scholar]
  44. Shaw G. M., Hahn B. H., Arya S. K., Groopman J. E., Gallo R. C., Wong-Staal F. 1984; Molecular characterization of human T-cell leukemia (lymphotropic) virus type III in the acquired immune deficiency syndrome. Science 226:1165–1171
     [Google Scholar]
  45. Sodroski J. G., Goh W. C., Rosen A., Campbell K., Haseltine W. A. 1986; Role of the HTLV/LAV envelope in syncytia formation and cytopathicity. Nature, London 322:470–474
     [Google Scholar]
  46. Somasundaran M., Robinson H. L. 1988; Unexpectedly high levels of HIV-1 RNA and protein synthesis in a cytocidal infection. Science 242:1554–1557
     [Google Scholar]
  47. Stevenson M., Meier C., Mann A. M., Chapman N., Wasiak A. 1988; Envelope glycoprotein of HIV induces interference and cytolysis resistance in CD4+ cells: mechanism for persistence in AIDS. Cell 53:483–496
     [Google Scholar]
  48. Terai C., Kornbluth R. S., Pauza C. D., Richman D. D., Carson D. A. 1991; Apoptosis as a mechanism of cell death in cultured T lymphoblasts acutely infected with HIV-1. Journal of Clinical Investigation 87:1710–1715
     [Google Scholar]
  49. Tersmette M., De Goede R. E. Y., Al B. J. M., Winkel I. N., Gruters R. A., Cuypers H. T., Huisman H. G., Miedema F. 1988; 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. Journal of Virology 62:2026–2032
     [Google Scholar]
  50. Varmus H., Swanstrom R. 1984; Replication of retroviruses. In RNA Tumor Viruses pp 369–512 Edited by Weiss R., Teich N., Varmus H., Coffin J. New York: Cold Spring Harbor Laboratory;
     [Google Scholar]
  51. Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M. 1985; Nucleotide sequence of the AIDS virus, LAV. Cell 40:9–17
     [Google Scholar]
  52. Wain-Hobson S., Vartanian J. P., Henry M., Chenciner N., Cheynier R., Delassus S., Martins L. P., Sala M., Nugeyre M. T., Guetard D., Klatzmann D., Gluckman J. C., Risenbaum W., Barre-Sinoussi F., Montagnier L. 1991; LAV revisited: origins of the early HIV-1 isolates from Institut Pasteur. Science 252:961–965
     [Google Scholar]
  53. Weller S. K., Joy A. E., Temin H. M. 1980; Correlation between cell killing and massive second-round superinfection by members of some subgroups of avian leukosis virus. Journal of Virology 33:494–506
     [Google Scholar]
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The cytopathic effect of human immunodeficiency virus is independent of high levels of unintegrated viral DNA accumulated in response to superinfection of cells
J. Gen. Virol. 74, 2619 (1993); https://doi.org/10.1099/0022-1317-74-12-2619
/content/journal/jgv/10.1099/0022-1317-74-12-2619
/content/journal/jgv/10.1099/0022-1317-74-12-2619
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