Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1986 Nov;78(5):1229–1236. doi: 10.1172/JCI112706

Humoral immune responses to T cell tropic retrovirus simian T lymphotropic virus type III in monkeys with experimentally induced acquired immune deficiency-like syndrome.

M Kannagi, M Kiyotaki, R C Desrosiers, K A Reimann, N W King, L M Waldron, N L Letvin
PMCID: PMC423808  PMID: 3771794

Abstract

The T cell tropic retrovirus of macaque monkeys simian T lymphotropic virus type III (STLV-III) has morphologic, growth, and antigenic properties indicating that it is related to human T cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV), the etiologic agent of the acquired immune deficiency syndrome (AIDS) of humans. STLV-III has recently been shown to induce an AIDS-like disease in macaque monkeys. In this study the humoral immune responses of six experimentally infected monkeys have been characterized to determine whether certain parameters of the antibody response to the virus might be predictive of the clinical outcome of this infection. Two distinct patterns of antibody responses were found. Four animals that died within 160 d of inoculation developed low titer anti-STLV-III antibody responses that recognized only the viral envelope protein, and progressive declines in total plasma IgG levels and absolute peripheral blood T4 lymphocyte numbers. The two animals that lived longer (one died at 352 d, the other remains alive at 430 d) developed high titer anti-STLV-III antibody responses that recognized both viral envelope and core proteins, increases in total plasma IgG, and a later decrease in number of peripheral blood T4 lymphocytes. Interestingly, the single animal that has remained clinically healthy after infection was the only one to develop detectable STLV-III neutralizing antibodies.

Full text

PDF
1229

Images in this article

1231Image
on p.1231
1231Image
on p.1231
1233Image
on p.1233
1233Image
on p.1233

Selected References

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

  1. Alter H. J., Eichberg J. W., Masur H., Saxinger W. C., Gallo R., Macher A. M., Lane H. C., Fauci A. S. Transmission of HTLV-III infection from human plasma to chimpanzees: an animal model for AIDS. Science. 1984 Nov 2;226(4674):549–552. doi: 10.1126/science.6093251. [DOI] [PubMed] [Google Scholar]
  2. Barin F., McLane M. F., Allan J. S., Lee T. H., Groopman J. E., Essex M. Virus envelope protein of HTLV-III represents major target antigen for antibodies in AIDS patients. Science. 1985 May 31;228(4703):1094–1096. doi: 10.1126/science.2986291. [DOI] [PubMed] [Google Scholar]
  3. Benn S., Rutledge R., Folks T., Gold J., Baker L., McCormick J., Feorino P., Piot P., Quinn T., Martin M. Genomic heterogeneity of AIDS retroviral isolates from North America and Zaire. Science. 1985 Nov 22;230(4728):949–951. doi: 10.1126/science.2997922. [DOI] [PubMed] [Google Scholar]
  4. Casey J. M., Kim Y., Andersen P. R., Watson K. F., Fox J. L., Devare S. G. Human T-cell lymphotropic virus type III: immunologic characterization and primary structure analysis of the major internal protein, p24. J Virol. 1985 Aug;55(2):417–423. doi: 10.1128/jvi.55.2.417-423.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Curran J. W., Morgan W. M., Hardy A. M., Jaffe H. W., Darrow W. W., Dowdle W. R. The epidemiology of AIDS: current status and future prospects. Science. 1985 Sep 27;229(4720):1352–1357. doi: 10.1126/science.2994217. [DOI] [PubMed] [Google Scholar]
  6. Daniel M. D., Letvin N. L., King N. W., Kannagi M., Sehgal P. K., Hunt R. D., Kanki P. J., Essex M., Desrosiers R. C. Isolation of T-cell tropic HTLV-III-like retrovirus from macaques. Science. 1985 Jun 7;228(4704):1201–1204. doi: 10.1126/science.3159089. [DOI] [PubMed] [Google Scholar]
  7. Fauci A. S., Masur H., Gelmann E. P., Markham P. D., Hahn B. H., Lane H. C. NIH conference. The acquired immunodeficiency syndrome: an update. Ann Intern Med. 1985 Jun;102(6):800–813. doi: 10.7326/0003-4819-102-6-800. [DOI] [PubMed] [Google Scholar]
  8. Gajdusek D. C., Amyx H. L., Gibbs C. J., Jr, Asher D. M., Rodgers-Johnson P., Epstein L. G., Sarin P. S., Gallo R. C., Maluish A., Arthur L. O. Infection of chimpanzees by human T-lymphotropic retroviruses in brain and other tissues from AIDS patients. Lancet. 1985 Jan 5;1(8419):55–56. doi: 10.1016/s0140-6736(85)91011-6. [DOI] [PubMed] [Google Scholar]
  9. Gajdusek D. C., Amyx H. L., Gibbs C. J., Jr, Asher D. M., Yanagihara R. T., Rodgers-Johnson P., Brown P. W., Sarin P. S., Gallo R. C., Jr, Maluish A. Transmission experiments with human T-lymphotropic retroviruses and human AIDS tissue. Lancet. 1984 Jun 23;1(8391):1415–1416. doi: 10.1016/s0140-6736(84)91916-0. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Kalyanaraman V. S., Cabradilla C. D., Getchell J. P., Narayanan R., Braff E. H., Chermann J. C., Barré-Sinoussi F., Montagnier L., Spira T. J., Kaplan J. Antibodies to the core protein of lymphadenopathy-associated virus (LAV) in patients with AIDS. Science. 1984 Jul 20;225(4659):321–323. doi: 10.1126/science.6330889. [DOI] [PubMed] [Google Scholar]
  12. Kalyanaraman V. S., Cabradilla C. D., Getchell J. P., Narayanan R., Braff E. H., Chermann J. C., Barré-Sinoussi F., Montagnier L., Spira T. J., Kaplan J. Antibodies to the core protein of lymphadenopathy-associated virus (LAV) in patients with AIDS. Science. 1984 Jul 20;225(4659):321–323. doi: 10.1126/science.6330889. [DOI] [PubMed] [Google Scholar]
  13. Kanki P. J., McLane M. F., King N. W., Jr, Letvin N. L., Hunt R. D., Sehgal P., Daniel M. D., Desrosiers R. C., Essex M. Serologic identification and characterization of a macaque T-lymphotropic retrovirus closely related to HTLV-III. Science. 1985 Jun 7;228(4704):1199–1201. doi: 10.1126/science.3873705. [DOI] [PubMed] [Google Scholar]
  14. Kannagi M., Yetz J. M., Letvin N. L. In vitro growth characteristics of simian T-lymphotropic virus type III. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7053–7057. doi: 10.1073/pnas.82.20.7053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  16. Lane H. C., Fauci A. S. Immunologic abnormalities in the acquired immunodeficiency syndrome. Annu Rev Immunol. 1985;3:477–500. doi: 10.1146/annurev.iy.03.040185.002401. [DOI] [PubMed] [Google Scholar]
  17. Lane H. C., Masur H., Gelmann E. P., Longo D. L., Steis R. G., Chused T., Whalen G., Edgar L. C., Fauci A. S. Correlation between immunologic function and clinical subpopulations of patients with the acquired immune deficiency syndrome. Am J Med. 1985 Mar;78(3):417–422. doi: 10.1016/0002-9343(85)90332-8. [DOI] [PubMed] [Google Scholar]
  18. Letvin N. L., Daniel M. D., Sehgal P. K., Desrosiers R. C., Hunt R. D., Waldron L. M., MacKey J. J., Schmidt D. K., Chalifoux L. V., King N. W. Induction of AIDS-like disease in macaque monkeys with T-cell tropic retrovirus STLV-III. Science. 1985 Oct 4;230(4721):71–73. doi: 10.1126/science.2412295. [DOI] [PubMed] [Google Scholar]
  19. Letvin N. L., Goldmacher V. S., Ritz J., Yetz J. M., Schlossman S. F., Lambert J. M. In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates. In vivo stability of disulfide-linked immunotoxin conjugates. J Clin Invest. 1986 Mar;77(3):977–984. doi: 10.1172/JCI112399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McGrath M., Witte O., Pincus T., Weissman I. L. Retrovirus purification: method that conserves envelope glycoprotein and maximizes infectivity. J Virol. 1978 Mar;25(3):923–927. doi: 10.1128/jvi.25.3.923-927.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rasheed S., Norman G. L., Gill P. S., Meyer P. R., Cheng L., Levine A. M. Virus-neutralizing activity, serologic heterogeneity, and retrovirus isolation from homosexual men in the Los Angeles area. Virology. 1986 Apr 15;150(1):1–9. doi: 10.1016/0042-6822(86)90260-6. [DOI] [PubMed] [Google Scholar]
  22. Robert-Guroff M., Brown M., Gallo R. C. HTLV-III-neutralizing antibodies in patients with AIDS and AIDS-related complex. Nature. 1985 Jul 4;316(6023):72–74. doi: 10.1038/316072a0. [DOI] [PubMed] [Google Scholar]
  23. Sarngadharan M. G., Popovic M., Bruch L., Schüpbach J., Gallo R. C. Antibodies reactive with human T-lymphotropic retroviruses (HTLV-III) in the serum of patients with AIDS. Science. 1984 May 4;224(4648):506–508. doi: 10.1126/science.6324345. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Steimer K. S., Puma J. P., Power M. D., Powers M. A., George-Nascimento C., Stephans J. C., Levy J. A., Sanchez-Pescador R., Luciw P. A., Barr P. J. Differential antibody responses of individuals infected with AIDS-associated retroviruses surveyed using the viral core antigen p25gag expressed in bacteria. Virology. 1986 Apr 15;150(1):283–290. doi: 10.1016/0042-6822(86)90289-8. [DOI] [PubMed] [Google Scholar]
  26. Weiss R. A., Clapham P. R., Cheingsong-Popov R., Dalgleish A. G., Carne C. A., Weller I. V., Tedder R. S. Neutralization of human T-lymphotropic virus type III by sera of AIDS and AIDS-risk patients. Nature. 1985 Jul 4;316(6023):69–72. doi: 10.1038/316069a0. [DOI] [PubMed] [Google Scholar]
  27. 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]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES