Rhesus monkey macrophages infected with simian immunodeficiency virus cause rapid lysis of CD4-bearing lymphocytes Free

Abstract

Inoculation of simian immunodeficiency virus into cultures of primary rhesus monkey macrophages or CD4-bearing transformed T lymphocytes resulted in persistent infection, with minimal virus replication in the macrophages and extensive replication in the lymphocytes. However, uninfected T cells added to infected macrophages underwent rapid fusion and lysis and were almost completely eliminated without the production of virus particles. Lysis required direct contact between the T cells and the infected macrophages, which enabled binding between CD4 on the former and viral gp120 on the latter to occur. This process was blocked by soluble CD4 and dextran sulphate. Neutralizing antibodies in the serum of an infected macaque prevented cell fusion by preventing infection of the macrophages. However, these antibodies did not prevent fusion when added to previously infected macrophages. Infected macrophages were incorporated into the syncytia of lymphocytes and continued incorporation of new lymphocytes into the syncytia required infected macrophages to be metabolically active. One inference from these studies is that infected macrophages could help mediate the well known depletion of T4 cells in patients with AIDS.

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1991-02-01
2024-03-28
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References

  1. Clapham P. R., Weber J. N., Whitby D., McIntosh K., Dalgleish A. G., Maddon P. J., Deen K. C., Sweet R. W., Weiss R. A. 1989; Soluble CD4 blocks the infectivity of diverse strains of HIV and SIV for T cells and monocytes but not for brain and muscle cells. Nature, London 337:368–370
    [Google Scholar]
  2. Eilbott D. J., Peress N., Burger H., LaNeve D., Orenstein J., Gendelman H. E., Seidman R., Weiser B. 1989; Human immunodeficiency virus type 1 in spinal cords of acquired immunodeficiency syndrome patients with myelopathy: expression and replication in macrophages. Proceedings of the National Academy of Sciences, U,. S,. A. 86:3337–3341
    [Google Scholar]
  3. Fauci A. S. 1988; The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science 239:617–622
    [Google Scholar]
  4. Fisher R. A., Bertonis J. M., Meier W., Johnson V. A., Costopoulos D. S., Liu T., Tizard R., Walker B. D., Hirsch M. S., Schooley R. T., Flavell R. A. 1988; HIV infection is blocked in vitro by recombinant soluble CD4. Nature, London 331:76–78
    [Google Scholar]
  5. Fox C. H., Kotler D., Tierney A., Wilson C. S., Fauci A. S. 1989; Detection of HIV-1 RNA in the lamina propria of patients with AIDS and gastrointestinal disease. Journal of Infectious Diseases 159:467–471
    [Google Scholar]
  6. Gartner S., Markovits P., Markovitz D. M., Kaplan M. H., Gallo R. C., Popovic M. 1986a; The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 233:215–219
    [Google Scholar]
  7. Gartner S., Markovits P., Markovitz D. M., Betts R. F., Popovic M. 1986b; Virus isolation from and identification of HTLV-III/LAV-producing cells in brain tissue from a patient with AIDS. Journal of the American Medical Association 256:2365–2371
    [Google Scholar]
  8. Gendelman H. E., Moench T. R., Narayan O., Griffin D. E. 1983; Selection of a fixative for identifying T cell subsets, B cells, and macrophages in paraffin-embedded mouse spleen. Journal of Immunological Methods 65:137–145
    [Google Scholar]
  9. Gendelman H. E., Narayan O., Kennedy-Stoskopf S., Kennedy P. G. E., Ghotbi Z., Clements J. E., Stanley J., Pezeshka-Pour G. 1986; Tropism of sheep lentiviruses for monocytes: susceptibility to infection and virus gene expression increase during maturation of monocytes to macrophages. Journal of Virology 58:67–74
    [Google Scholar]
  10. Haase A. T., Stowring L., Harris J. D., Traynor B., Ventura P., Peluso R., Brahic M. 1982; Visna DNA synthesis and the tempo of infection in vitro . Virology 119:399–410
    [Google Scholar]
  11. Harper M. E., Marselle L. M., Gallo R. C., Wong-Staal F. 1986; Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. Proceedings of the National Academy of Sciences, U,. S,. A. 83:772–776
    [Google Scholar]
  12. Hart G. W. 1982; The role of asparagine-linked oligosaccharides in cellular recognition by thymic lymphocytes. Journal of Biological Chemistry 257:151–158
    [Google Scholar]
  13. Harter D. H., Choppin R. C. 1967; Cell fusion activity of visna virus particles. Virology 31:279–288
    [Google Scholar]
  14. Hoxie J. A., Levy J. A. 1989; Mechanism of CD4+ cell killing by the human immunodeficiency virus. In Concepts in Viral Pathogenesis vol III pp. 215–224 Edited by Notkins A. L., Oldstone M. B. A. New York: Springer-Verlag;
    [Google Scholar]
  15. Hoxie J. A., Alpers J. D., Rackowski J. L., Huebner K., Haggarty B. S., Cedarbaum A. J., Reed J. C. 1986; Alterations in T4 (CD4) protein and mRNA synthesis in cells infected with HIV. Science 234:1123–1127
    [Google Scholar]
  16. Hoxie J. A., Haggarty B. S., Bonser S. E., Rackowski J. L., Shan H., Kanki P. J. 1988; Biological characterization of a simian immunodeficiency virus-like retrovirus (HTLV-IV): evidence for CD4-associated molecules required for infection. Journal of Virology 62:2557–2568
    [Google Scholar]
  17. Hussey R. E., Richardson N. E., Kowalski M., Brown N. R., Chang H. C., Siliciano R. F., Dorfman T., Walker B., Sodroski J., Reinherz E. L. 1988; A soluble CD4 protein selectively inhibits HIV replication and syncytium formation. Nature, London 331:78–81
    [Google Scholar]
  18. Kennedy P. G. E., Narayan O., Ghotbi Z., Hopkins J., Gendelman H., Clements J. E. 1985; Persistent expression of la antigen on viral genome in visna-maedi virus-induced inflammatory cells. Possible role of lentivirus induced interferon. Journal of Experimental Medicine 162:1970–1982
    [Google Scholar]
  19. Koenig S., Gendelman H. E., Orenstein J. M., Dal Canto M. C., Pezeshkpour G. H., Yungbluth M., JaNOtta F., Aksamit A., Martin M. A., Fauci A. S. 1986; Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science 233:1089–1093
    [Google Scholar]
  20. Koenig S., Hirsch V. M., Olmsted R. A., Powell D., Maury W., Rabson A., Fauci A. S., Purcell R. H., Johnson P. R. 1989; Selective infection of human CD4+ cells by simian immunodeficiency virus: productive infection associated with envelope glycoprotein induced fusion. Proceedings of the National Academy of Sciences, U,. S,. A. 86:2443–2447
    [Google Scholar]
  21. Kowalski M., Potz J., Basiripour L., Dorfman T., Goh W. C., Terwilliger E., Dayton A., Rosen C., Haseltine W., Sodroski J. 1987; Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1. Science 237:1351–1355
    [Google Scholar]
  22. L’Age-Stehr J., Niedrig M., Gelderblom H. R., Sim-Brandenburg J. W., Urban-Schriefer M., Rieber E. P., Haas J. C., Riethmuller G., Ziegler-Heitbrock H. W. L. 1990; Infection of the human monocytic cell line mono Mac6 with human immunodeficiency virus types 1 and 2 results in long-term production of virus variants with increased cytopathogenicity for CD4+ T cells. Journal of Virology 64:3982–3987
    [Google Scholar]
  23. Lasky L. A., Nakamura G., Smith D. H., Fennie C., Shimasaki C., Patzer E., Berman P., Gregory T., Capon D. J. 1987; Delineation of a region of the human immunodeficiency virus type I (HIV-I) gp120 glycoprotein critical for interaction with the CD4 receptor. Cell 50:975–985
    [Google Scholar]
  24. Lifson J. D., Reyes G. R., McGrath M. S., Stein B. S., Engelman E. G. 1986; AIDS retrovirus induced cytopathology. giant cell formation and involvement of CD4 antigen. Science 232:1123–1127
    [Google Scholar]
  25. McCune J. M., Rabin L. B., Feinberg M. B., Lieberman M., Kosek J. C., Reyes G. R., Weissman I. L. 1988; Endoproteolytic cleavage of gp160 is required for the activation of human immunodeficiency virus. Cell 53:55–57
    [Google Scholar]
  26. Mitsuya H., Looney D. J., Kuno S., Ueno R., Wong-Staal F., Broder S. 1989; Dextran sulfate suppression of viruses in the HIV family: inhibition of virion binding to CD4+ cells. Science 240:646–649
    [Google Scholar]
  27. Narayan O. 1990; Lentiviruses are etioiogical agents of chronic diseases in animals and acquired immunodeficiency in humans. Canadian Journal of Veterinary Research 54:42–48
    [Google Scholar]
  28. Narayan O., Clements J. E. 1989; Biology and pathogenesis of lentiviruses. Journal of General Virology 70:1617–1639
    [Google Scholar]
  29. Narayan O., Wolinsky J. S., Clements J. E., Strandberg J. D., Griffin D. E., Cork L. C. 1982; Slow virus replication: the role of macrophages in the persistence and expression of visna viruses of sheep and goats. Journal of General Virology 59:345–356
    [Google Scholar]
  30. Narayan O., Sheffer D., Clements J. E., Tennekoon G. 1985; Restricted replication of lentiviruses: visna viruses induce a unique interferon during interaction between lymphocytes and infected macrophages. Journal of Experimental Medicine 162:1954–1969
    [Google Scholar]
  31. Peluso R., Haase A., Stowring L., Edwards M., Ventura P. 1985; A Trojan horse mechanism for the spread of visna virus in monocytes. Virology 147:231
    [Google Scholar]
  32. Ringler D. J., Wyand M. S., Walsh D. G., MacKey J. J., Chalifoux L. V., Popovic M., Minassian A. A., Sehgal P. K., Daniel M. D., Desrosiers R. C., King N. W. 1989; Cellular localization of simian immunodeficiency virus in lymphoid tissues. I. Immunohistochemistry and electron microscopy. American Journal of Pathology 134:373–383
    [Google Scholar]
  33. Schnittman S. M., Psallidopoulos M. C., Lane H. C., Thompson L., Baseler M., Massari F., Fox C. H., Salzman N. P., Fauci A. S. 1989; The reservoir for HIV-1 in human peripheral blood is a T cell that maintains expression of CD4. Science 245:305–308
    [Google Scholar]
  34. Sodroski J., Goh W. C., Rosen C., Campbell K., Haseltine W. A. 1986; Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity. Nature, London 322:470–474
    [Google Scholar]
  35. Stein B. S., Cowda S. D., Lifson J. D., Penhallow R. C., Bensch K. G., Engelman E. G. 1987; pH-independent HIV entry into CD4-positive T cells via virus envelope fusion to the plasma membrane. Cell 49:659–668
    [Google Scholar]
  36. Stoler M. H., Eskin T. A., Benn S., Angerer R. C., Angerer L. M. 1986; Human T-cell lymphotropic virus type III infection of the central nervous system. A preliminary in situ analysis. Journal of the American Medical Association 256:2360–2364
    [Google Scholar]
  37. Ward J. M., O’Leary T. J., Baskin G. B., Benveniste R., Harris C. A., Nara P. L., Rhodes R. H. 1987; Immunohistochemical localization of human and simian immunodeficiency viral antigens in fixed tissue sections. American Journal of Pathology 127:199–205
    [Google Scholar]
  38. Watanabe M., Reimann K. A., DeLong P. A., Liu T., Fisher R. A., Letvin N. L. 1989; Effect of recombinant soluble CD4 in rhesus monkeys infected with simian immunodeficiency virus of macaques. Nature, London 337:267–270
    [Google Scholar]
  39. Wiley C. A., Schrier R. D., Nelson J. A., Lampert P. W., Oldstone M. B. A. 1986; Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proceedings of the National Academy of Sciences, U,. S,. A 83:7089–7093
    [Google Scholar]
  40. Wyand M. S., Ringler D. J., Naidu Y. M., Mattmuller M., Chalifoux L. V., Sehgal P. K., Daniel M. D., Desrosiers R. C., King N. W. 1989; Cellular localization of simian immunodeficiency virus in lymphoid tissues. II. In situ hybridization. American Journal of Pathology 134:385–393
    [Google Scholar]
  41. Zink M. C., Narayan O. 1989; Lentivirus-induced interferon inhibits maturation and proliferation of monocytes and restricts the replication of caprine arthritis-encephalitis virus. Journal of Virology 63:2578–2584
    [Google Scholar]
  42. Zink M. C., Yager J. A., Myers J. D. 1990; Pathogenesis of caprine arthritis encephalitis virus: cellular localization of viral transcripts in tissues of infected goats. American Journal of Pathology 136:843–854
    [Google Scholar]
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