1887

Abstract

Survival of rhesus macaques () experimentally infected with simian immunodeficiency virus (SIV) varies significantly from animal to animal. Some animals die within 2 months while others survive for more than 5 years, even when identical inocula are used. This diversity in survival creates a significant problem in the design of therapeutic and vaccine trials using the SIV–macaque model because the use of small numbers of animals may provide results that are misleading. Identifying an assay that could determine the survival of monkeys prior to infection would prove extremely useful for stratifying experimental groups. Analysis of the survival of a cohort of 59 control animals obtained from over a decade of vaccine and therapeutic trials has demonstrated that the ability of peripheral blood mononuclear cells (PBMC) from a naı̈ve animal to produce virus was highly predictive of disease progression following experimental inoculation. Animals classified as high producers of virus progressed to disease significantly more rapidly than animals classified as either low (=0·002) or intermediate (=0·013) producers of virus. The hierarchy of high and low virus production was maintained in purified CD4 T cell cultures, indicating that this phenotype is an intrinsic property of the CD4 T cell itself. These findings should significantly aid in the design of vaccine and therapeutic trials using the SIV–macaque model. Furthermore, since these studies suggest that the rate of virus replication is controlled by innate characteristics of the individual, they provide new insight into the pathogenesis of AIDS.

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2000-10-01
2020-01-28
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References

  1. Buchbinder, S. P., Katz, M. H., Hessol, N. A., O’Malley, P. M. & Holmberg, S. D. ( 1994; ). Long-term HIV-1 infection without immunologic progression. AIDS 8, 1123-1128.[CrossRef]
    [Google Scholar]
  2. Cao, Y., Qin, L., Zhang, L., Safrit, J. & Ho, D. D. ( 1995; ). Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. New England Journal of Medicine 322, 201-208.
    [Google Scholar]
  3. Dittmer, U., Luke, W., Stahl-Hennig, C., Coulibaly, C., Petry, H., Bodemer, W., Hunsmann, G. & Voss, G. ( 1994; ). Early helper T cell dysfunction in SIV-but not HIV-2-infected macaques. Journal of Medical Primatology 23, 298-303.[CrossRef]
    [Google Scholar]
  4. Dykhuizen, M., Mitchen, J. L., Montefiori, D. C., Thomson, J., Acker, L., Lardy, H. & Pauza, C. D. ( 1998; ). Determinants of disease in the simian immunodeficiency virus-infected rhesus macaque: characterizing animals with low antibody responses and rapid progression. Journal of General Virology 79, 2461-2467.
    [Google Scholar]
  5. Farzadegan, H., Henrard, D. R., Kleeberger, C. A., Schrager, L., Kirby, A. J., Saah, A. J., Rinaldo, C. R.Jr, O’Gorman, M., Detels, R., Taylor, E., Phair, J. P. & Margolick, J. B. ( 1996; ). Virologic and serologic markers of rapid progression to AIDS after HIV-1 seroconversion. Journal of Acquired Immune Deficiency Syndromes 13, 448-455.[CrossRef]
    [Google Scholar]
  6. Habis, A., Baskin, G. B., Murphey-Corb, M. & Levy, L. S. ( 1999; ). SAIDS-associated lymphoma (SAL) in rhesus and cynomolgus monkeys recapitulates the primary pathobiological features of AIDS-associated non-Hodgkin’s lymphoma (AAL). AIDS Research and Human Retroviruses 15, 1389-1398.[CrossRef]
    [Google Scholar]
  7. Haynes, B. F., Pantaleo, G. & Fauci, A. S. ( 1996; ). Toward an understanding of the correlates of protective immunity to HIV infection. Science 271, 324-328.[CrossRef]
    [Google Scholar]
  8. Kindt, T. J., Hirsch, V. M., Johnson, P. R. & Sawasdikosol, S. ( 1992; ). Animal models for acquired immunodeficiency syndrome. Advances in Immunology 52, 425-474.
    [Google Scholar]
  9. Lackner, A. ( 1994; ). Pathology of simian immunodeficiency virus infection. Current Topics in Microbiology and Immunology 188, 35-64.
    [Google Scholar]
  10. Letvin, N. L. & King, N. W. ( 1990; ). Immunologic and pathologic manifestations of the infection of rhesus monkeys with simian immunodeficiency virus of macaques. Journal of Acquired Immune Deficiency Syndromes 3, 1023-1040.
    [Google Scholar]
  11. Lifson, A. R., Rutherford, G. W. & Jaffe, H. W. ( 1988; ). The natural history of human immunodeficiency virus infection. Journal of Infectious Diseases 158, 1360-1367.[CrossRef]
    [Google Scholar]
  12. Lifson, J. D., Nowak, M. A., Goldstein, S., Rossio, J. L., Kinter, A., Vasquez, G., Wiltrout, T. A., Brown, C., Schneider, D., Wahl, L., Lloyd, A. L., Williams, J., Elkins, W. R., Fauci, A. S. & Hirsch, V. M. ( 1997; ). The extent of early viral replication is a critical determinant of the natural history of simian immunodeficiency virus infection. Journal of Virology 71, 9508-9514.
    [Google Scholar]
  13. Liu, S. L., Schacker, T., Musey, L., Shriner, D., McElrath, M. J., Corey, L. & Mullins, J. I. ( 1997; ). Divergent patterns of progression to AIDS after infection from the same source: human immunodeficiency virus type 1 evolution and antiviral responses. Journal of Virology 71, 4284-4295.
    [Google Scholar]
  14. Martin, L. N., Murphey-Corb, M., Soike, K. F., Davison-Fairburn, B. & Baskin, G. B. ( 1993; ). Effects of initiation of 3′-azido,3′-deoxythymidine (zidovudine) treatment at different times after infection of rhesus monkeys with simian immunodeficiency virus. Journal of Infectious Diseases 168, 825-835.[CrossRef]
    [Google Scholar]
  15. Martin, L. N., Soike, K. F., Murphey-Corb, M., Bohn, R. P., Roberts, E. D., Kakuk, T. J., Thaisrivongs, S., Vidmar, T. J., Ruwart, M. J., Davio, S. R. & Tarpley, W. G. ( 1994; ). Effects of U-75875, a peptidomimetic inhibitor of retroviral proteases, on simian immunodeficiency virus infection in rhesus monkeys. Antimicrobial Agents and Chemotherapy 38, 1277-1283.[CrossRef]
    [Google Scholar]
  16. Martin, L. N., Murphey-Corb, M., Mack, P., Baskin, G. B., Pantaleo, G., Vaccarezza, M., Fox, C. H. & Fauci, A. S. ( 1997; ). Cyclosporin: a modulation of early virologic and immunologic events during primary simian immunodeficiency virus infection in rhesus monkeys. Journal of Infectious Diseases 176, 374-383.[CrossRef]
    [Google Scholar]
  17. Michael, N. L., Brown, A. E., Voigt, R. F., Frankel, S. S., Mascola, J. R., Brothers, K. S., Louder, M., Birx, D. L. & Cassol, S. A. ( 1997; ). Rapid disease progression without seroconversion following primary human immunodeficiency type 1 infection – evidence for highly susceptible human hosts. Journal of Infectious Diseases 174, 1352-1359.
    [Google Scholar]
  18. Munoz, A., Wang, M. C., Bass, S., Taylor, J. M., Kingsley, L. A., Chmiel, J. S. & Polk, B. F. ( 1989; ). Acquired immunodeficiency syndrome (AIDS)-free time after human immunodeficiency virus type 1 (HIV-1) seroconversion in homosexual men. American Journal of Epidemiology 130, 530-539.
    [Google Scholar]
  19. Munoz, A., Kirby, A. J., He, Y. D., Margolick, J. B., Visscher, B. R., Rinaldo, C. R., Kaslow, R. A. & Phair, J. P. ( 1995; ). Long-term survivors with HIV-1 infection: incubation period and longitudinal patterns of CD4+ lymphocytes. Journal of Acquired Immune Deficiency Syndromes 8, 496-505.[CrossRef]
    [Google Scholar]
  20. Murphey-Corb, M., Martin, L. N., Rangan, S. R. S., Baskin, G. B., Gormus, B. J., Wolf, R. H., Andes, W. A., West, M. & Montelaro, R. C. ( 1986; ). Isolation of an HTLV-III-related retrovirus from macaques with simian AIDS and its possible origin in asymptomatic mangabeys. Nature 321, 435-437.[CrossRef]
    [Google Scholar]
  21. Murphey-Corb, M., Martin, L. & Davison-Fairburn, B. (1989). The susceptibility of rhesus PBL to SIV/Delta infection in vitro is predictive of in vivo disease. 8th Annual Symposium on Non-human Primate Models for AIDS.
  22. Nicholson, J. K., Spira, T. J., Aloisio, C. H., Jones, B. M., Kennedy, M. S., Holman, R. C. & McDougal, J. S. ( 1989; ). Serial determinations of HIV-1 titers in HIV-infected homosexual men: association of rising titers with CD4 T cell depletion and progression to AIDS. AIDS Research and Human Retroviruses 5, 205-215.[CrossRef]
    [Google Scholar]
  23. O’Brien, T., Blattner, W. A., Waters, D., Eyster, E., Hilgartner, M. W., Cohen, A. R., Luban, N., Hatzakis, A., Aledort, L. M., Rosenberg, P. S., Miley, W. J., Kroner, B. L. & Goedert, J. J. ( 1996; ). Serum HIV-1 RNA levels and time to development of AIDS in the multicenter hemophilia cohort study. Journal of the American Medical Association 276, 105-110.[CrossRef]
    [Google Scholar]
  24. Operskalski, E. A., Busch, M. P., Mosley, J. W., Stram, D. O. & Transfusion Study Safety Group ( 1997; ). Comparative rates of disease progression among persons infected with the same or different HIV-1 strains. Journal of Acquired Immune Deficiency Syndromes 15, 145–150.[CrossRef]
    [Google Scholar]
  25. Williams, L. M. & Cloyd, M. W. ( 1991; ). Polymorphic human gene(s) determines differential susceptibility of CD4 lymphocytes to infection by certain HIV-1 isolates. Virology 184, 723-728.[CrossRef]
    [Google Scholar]
  26. Zhang, J. Y., Martin, L. N., Watson, E. A., Montelaro, R. C., West, M., Epstein, L. & Murphey-Corb, M. ( 1988; ). Simian immunodeficiency virus/delta-induced immunodeficiency disease in rhesus monkeys: relation of antibody response and antigenemia. Journal of Infectious Diseases 158, 1277-1286.[CrossRef]
    [Google Scholar]
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