Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Jun;84(11):3797–3801. doi: 10.1073/pnas.84.11.3797

Absence of cytotoxic antibody to human immunodeficiency virus-infected cells in humans and its induction in animals after infection or immunization with purified envelope glycoprotein gp120.

P L Nara, W G Robey, M A Gonda, S G Carter, P J Fischinger
PMCID: PMC304963  PMID: 3473484

Abstract

The presence of antibody-dependent complement-mediated cytotoxicity (ACC) was assessed in humans and chimpanzees, which are capable of infection with human immunodeficiency virus isolate HTLV-IIIb, and examined in the goat after immunization with the major viral glycoprotein (gp120) of HTLV-IIIb. In infected humans no antibody mediating ACC was observed regardless of the status of disease. Even healthy individuals with high-titer, broadly reactive, neutralizing antibodies had no ACC. In contrast, chimpanzees infected with HTLV-IIIb, from whom virus could be isolated, not only had neutralizing antibody but also antibodies broadly reactive in ACC, even against distantly related human immunodeficiency virus isolates, as well as against their own reisolated virus. In the goat, the gp120 of HTLV-IIIb induced a highly type-specific response as measured by both ACC and flow cytofluorometry of live infected H9 cells. Normal human cells were not subject to ACC by animal anti-HTLV-III gp120-specific sera. Induction of ACC and neutralizing antibody were closely correlated in the animal experimental models but not in humans. The presence of ACC in gp120-inoculated goats and HTLV-III-infected chimpanzees represents a qualitative difference that may be important in the quest for the elicitation of a protective immunity in humans.

Full text

PDF
3797

Selected References

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

  1. Banapour B., Sernatinger J., Levy J. A. The AIDS-associated retrovirus is not sensitive to lysis or inactivation by human serum. Virology. 1986 Jul 15;152(1):268–271. doi: 10.1016/0042-6822(86)90392-2. [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. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  4. Fischinger P. J., Peebles P. T., Nomura S., Haapala D. K. Isolation of RD-114-like oncornavirus from a cat cell line. J Virol. 1973 Jun;11(6):978–985. doi: 10.1128/jvi.11.6.978-985.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fischinger P. J., Sch5AAFER W., Bolognesi D. P. Neutralization of homologous and heterologous oncornaviruses by antisera against the p15(E) and gp71 polypeptides of Friend murine leukemia virus. Virology. 1976 May;71(1):169–184. doi: 10.1016/0042-6822(76)90103-3. [DOI] [PubMed] [Google Scholar]
  6. Fultz P. N., McClure H. M., Swenson R. B., McGrath C. R., Brodie A., Getchell J. P., Jensen F. C., Anderson D. C., Broderson J. R., Francis D. P. Persistent infection of chimpanzees with human T-lymphotropic virus type III/lymphadenopathy-associated virus: a potential model for acquired immunodeficiency syndrome. J Virol. 1986 Apr;58(1):116–124. doi: 10.1128/jvi.58.1.116-124.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Gendelman H. E., Narayan O., Kennedy-Stoskopf S., Kennedy P. G., Ghotbi Z., Clements J. E., Stanley J., Pezeshkpour G. Tropism of sheep lentiviruses for monocytes: susceptibility to infection and virus gene expression increase during maturation of monocytes to macrophages. J Virol. 1986 Apr;58(1):67–74. doi: 10.1128/jvi.58.1.67-74.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Grant C. K., Essex M., Pedersen N. C., Hardy W. D., Jr, Stephenson J. R., Cotter S. M., Theilen G. H. Lysis of feline lymphoma cells by complement-dependent antibodies in feline leukemia virus contact cats. Correlation of lysis and antibodies to feline oncornavirus-associated cell membrane antigen. J Natl Cancer Inst. 1978 Jan;60(1):161–166. doi: 10.1093/jnci/60.1.161. [DOI] [PubMed] [Google Scholar]
  10. Grant C. K., Essex M., Pedersen N. C., Hardy W. D., Jr, Stephenson J. R., Cotter S. M., Theilen G. H. Lysis of feline lymphoma cells by complement-dependent antibodies in feline leukemia virus contact cats. Correlation of lysis and antibodies to feline oncornavirus-associated cell membrane antigen. J Natl Cancer Inst. 1978 Jan;60(1):161–166. doi: 10.1093/jnci/60.1.161. [DOI] [PubMed] [Google Scholar]
  11. Grant C. K., Worley M. B., DeBoer D. J. Detection of complement-dependent lytic antibodies in sera from feline leukemia virus-infected cats by the chromium-51 release assay. J Natl Cancer Inst. 1977 Jan;58(1):157–161. doi: 10.1093/jnci/58.1.157. [DOI] [PubMed] [Google Scholar]
  12. Hahn B. H., Shaw G. M., Taylor M. E., Redfield R. R., Markham P. D., Salahuddin S. Z., Wong-Staal F., Gallo R. C., Parks E. S., Parks W. P. Genetic variation in HTLV-III/LAV over time in patients with AIDS or at risk for AIDS. Science. 1986 Jun 20;232(4757):1548–1553. doi: 10.1126/science.3012778. [DOI] [PubMed] [Google Scholar]
  13. Hoshino H., Tanaka H., Miwa M., Okada H. Human T-cell leukaemia virus is not lysed by human serum. 1984 Jul 26-Aug 1Nature. 310(5975):324–325. doi: 10.1038/310324a0. [DOI] [PubMed] [Google Scholar]
  14. Hunsmann G., Claviez M., Moennig V., Schwarz H., Schäfer W. Properties of mouse leukemia viruses. X. Occurrence of viral structural antigens on the cell surface as revealed by a cytotoxicity test. Virology. 1976 Jan;69(1):157–168. doi: 10.1016/0042-6822(76)90203-8. [DOI] [PubMed] [Google Scholar]
  15. Kennedy-Stoskopf S., Narayan O. Neutralizing antibodies to visna lentivirus: mechanism of action and possible role in virus persistence. J Virol. 1986 Jul;59(1):37–44. doi: 10.1128/jvi.59.1.37-44.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lerner R. A., Oldstone M. B., Cooper N. R. Cell cycle-dependent immune lysis of Moloney virus-transformed lymphocytes: presence of viral antigen, accessibility to antibody, and complement activation. Proc Natl Acad Sci U S A. 1971 Oct;68(10):2584–2588. doi: 10.1073/pnas.68.10.2584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mathes L. E., Yohn D. S., Hoover E. A., Essex M., Schaller J. P., Olsen R. G. Feline oncornavirus-associated cell membrane antigen. VI. Cytotoxic antibody in cats exposed to feline leukemia virus. J Natl Cancer Inst. 1976 Jun;56(6):1197–1200. doi: 10.1093/jnci/56.6.1197. [DOI] [PubMed] [Google Scholar]
  18. Matthews T. J., Langlois A. J., Robey W. G., Chang N. T., Gallo R. C., Fischinger P. J., Bolognesi D. P. Restricted neutralization of divergent human T-lymphotropic virus type III isolates by antibodies to the major envelope glycoprotein. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9709–9713. doi: 10.1073/pnas.83.24.9709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Minowada J., Onuma T., Moore G. E. Rosette-forming human lymphoid cell lines. I. Establishment and evidence for origin of thymus-derived lymphocytes. J Natl Cancer Inst. 1972 Sep;49(3):891–895. [PubMed] [Google Scholar]
  20. Nara P. L., Robey W. G., Arthur L. O., Gonda M. A., Asher D. M., Yanagihara R., Gibbs C. J., Jr, Gajdusek D. C., Fischinger P. J. Simultaneous isolation of simian foamy virus and HTLV-III/LAV from chimpanzee lymphocytes following HTLV-III or LAV inoculation. Arch Virol. 1987;92(1-2):183–186. doi: 10.1007/BF01310072. [DOI] [PubMed] [Google Scholar]
  21. Onuma M., Olson C., Driscoll D. M. Properties of two isolated antigens associated with bovine leukemia virus infection. J Natl Cancer Inst. 1976 Sep;57(3):571–578. doi: 10.1093/jnci/57.3.571. [DOI] [PubMed] [Google Scholar]
  22. Peluso R., Haase A., Stowring L., Edwards M., Ventura P. A Trojan Horse mechanism for the spread of visna virus in monocytes. Virology. 1985 Nov;147(1):231–236. doi: 10.1016/0042-6822(85)90246-6. [DOI] [PubMed] [Google Scholar]
  23. Peters C. J., Theofilopoulos A. N. Antibody-dependent cellular cytotoxicity against murine leukemia viral antigens: studies with human lymphoblastoid cell lines and human peripheral lymphocytes as effector cells comparing rabbit, goat, and mouse antisera. J Immunol. 1977 Sep;119(3):1089–1096. [PubMed] [Google Scholar]
  24. Popovic M., Sarngadharan M. G., Read E., Gallo R. C. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. doi: 10.1126/science.6200935. [DOI] [PubMed] [Google Scholar]
  25. Robbins E. Cell synchronization. Methods Enzymol. 1974;32:592–597. [PubMed] [Google Scholar]
  26. Robey W. G., Arthur L. O., Matthews T. J., Langlois A., Copeland T. D., Lerche N. W., Oroszlan S., Bolognesi D. P., Gilden R. V., Fischinger P. J. Prospect for prevention of human immunodeficiency virus infection: purified 120-kDa envelope glycoprotein induces neutralizing antibody. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7023–7027. doi: 10.1073/pnas.83.18.7023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Robey W. G., Safai B., Oroszlan S., Arthur L. O., Gonda M. A., Gallo R. C., Fischinger P. J. Characterization of envelope and core structural gene products of HTLV-III with sera from AIDS patients. Science. 1985 May 3;228(4699):593–595. doi: 10.1126/science.2984774. [DOI] [PubMed] [Google Scholar]
  28. Safai B., Sarngadharan M. G., Groopman J. E., Arnett K., Popovic M., Sliski A., Schüpbach J., Gallo R. C. Seroepidemiological studies of human T-lymphotropic retrovirus type III in acquired immunodeficiency syndrome. Lancet. 1984 Jun 30;1(8392):1438–1440. doi: 10.1016/s0140-6736(84)91933-0. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Schlager S. I., Adams A. C. Use of dyes and radioisotopic markers in cytotoxicity tests. Methods Enzymol. 1983;93:233–245. doi: 10.1016/s0076-6879(83)93045-8. [DOI] [PubMed] [Google Scholar]
  31. Schäfer W., Bolognesi D. P. Mammalian C-type oncornaviruses: relationships between viral structural and cell-surface antigens and their possible significance in immunological defense mechanisms. Contemp Top Immunobiol. 1977;6:127–167. doi: 10.1007/978-1-4684-3051-6_4. [DOI] [PubMed] [Google Scholar]
  32. Schüpbach J., Popovic M., Gilden R. V., Gonda M. A., Sarngadharan M. G., Gallo R. C. Serological analysis of a subgroup of human T-lymphotropic retroviruses (HTLV-III) associated with AIDS. Science. 1984 May 4;224(4648):503–505. doi: 10.1126/science.6200937. [DOI] [PubMed] [Google Scholar]
  33. Sepulveda C. A., Schlager S. I. Poly-L-lysine-induced immobilization of tumor cells to plastic for the study of cellular metabolic responses to attack by cytotoxic T lymphocytes. Methods Enzymol. 1983;93:260–270. doi: 10.1016/s0076-6879(83)93048-3. [DOI] [PubMed] [Google Scholar]
  34. Sissons J. G., Oldstone M. B. Antibody-mediated destruction of virus-infected cells. Adv Immunol. 1980;29:209–260. doi: 10.1016/S0065-2776(08)60045-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Tam M. R., Green W. R., Nowinski R. C. Cytotoxic activities of monoclonal antibodies against the envelope proteins of murine leukemia virus. Cancer Res. 1980 Oct;40(10):3850–3853. [PubMed] [Google Scholar]
  36. Tam M. R., Green W. R., Nowinski R. C. Cytotoxic activities of monoclonal antibodies against the envelope proteins of murine leukemia virus. Cancer Res. 1980 Oct;40(10):3850–3853. [PubMed] [Google Scholar]
  37. Vedbrat S. S., Rasheed S., Lutz H., Gonda M. A., Ruscetti S., Gardner M. B., Prensky W. Feline oncornavirus-associated cell membrane antigen: a viral and not a cellularly coded transformation-specific antigen of cat lymphomas. Virology. 1983 Jan 30;124(2):445–461. doi: 10.1016/0042-6822(83)90360-4. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES