Abstract
Following natural and experimental infection by simian immunodeficiency virus SIVagm of African green monkeys (AGMs), the natural host, there is no evidence for the development of an immunodeficiency. Within the framework of our studies on human immunodeficiency virus (HIV)/SIV pathogenesis, we investigated the influence of CD8 T lymphocytes on SIVagm replication in AGM CD4 T lymphocytes in vitro. The following observations were made: (i) Peripheral blood mononuclear cells from both seronegative and seropositive AGMs contained only a low proportion (i.e., 10%) of CD4+ lymphocytes, whereas a high proportion (80%) of CD8+ cells was detected. Even after persistent SIVagm infection, CD4 T lymphocytes do not decrease in number. (ii) The target of in vitro infection of peripheral blood cells is the CD4+ mononuclear cell (T lymphocytes, monocytes) and SIVagm infects by binding to the CD4 molecule. (iii) In both naturally and experimentally SIVagm-infected AGMs the CD4+ T cells and monocytes, but not the CD8+ T cells, harbor DNA provirus. (iv) Virus reisolation and virus replication of SIVagm in CD4 T lymphocytes from seropositive AGMs is suppressed in the presence of autologous CD8 T lymphocytes or a soluble factor produced by these cells. Taken together, one possible reason for the apathogenicity of the SIVagm infection in AGMs may be the suppression of virus replication by a soluble, yet unidentified factor secreted by CD8 lymphocytes quantitatively dominating among peripheral blood cell populations. We have tentatively termed this factor "immunodeficiency virus-suppressing lymphokine." In addition, we show that immunodeficiency virus-suppressing lymphokine from AGMs is able to suppress HIV-1 replication in human CD4+ T cells.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baier M., Dittmar M. T., Cichutek K., Kurth R. Development of vivo of genetic variability of simian immunodeficiency virus. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8126–8130. doi: 10.1073/pnas.88.18.8126. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baier M., Garber C., Müller C., Cichutek K., Kurth R. Complete nucleotide sequence of a simian immunodeficiency virus from African green monkeys: a novel type of intragroup divergence. Virology. 1990 May;176(1):216–221. doi: 10.1016/0042-6822(90)90246-n. [DOI] [PubMed] [Google Scholar]
- Baier M., Werner A., Cichutek K., Garber C., Müller C., Kraus G., Ferdinand F. J., Hartung S., Papas T. S., Kurth R. Molecularly cloned simian immunodeficiency virus SIVagm3 is highly divergent from other SIVagm isolates and is biologically active in vitro and in vivo. J Virol. 1989 Dec;63(12):5119–5123. doi: 10.1128/jvi.63.12.5119-5123.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Binninger D., Ennen J., Bonn D., Norley S. G., Kurth R. Mutational analysis of the simian immunodeficiency virus SIVmac nef gene. J Virol. 1991 Oct;65(10):5237–5243. doi: 10.1128/jvi.65.10.5237-5243.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brinchmann J. E., Albert J., Vartdal F. Few infected CD4+ T cells but a high proportion of replication-competent provirus copies in asymptomatic human immunodeficiency virus type 1 infection. J Virol. 1991 Apr;65(4):2019–2023. doi: 10.1128/jvi.65.4.2019-2023.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Castro B. A., Walker C. M., Eichberg J. W., Levy J. A. Suppression of human immunodeficiency virus replication by CD8+ cells from infected and uninfected chimpanzees. Cell Immunol. 1991 Jan;132(1):246–255. doi: 10.1016/0008-8749(91)90023-5. [DOI] [PubMed] [Google Scholar]
- Cichutek K., Merget H., Norley S., Linde R., Kreuz W., Gahr M., Kurth R. Development of a quasispecies of human immunodeficiency virus type 1 in vivo. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7365–7369. doi: 10.1073/pnas.89.16.7365. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Coombs R. W., Collier A. C., Allain J. P., Nikora B., Leuther M., Gjerset G. F., Corey L. Plasma viremia in human immunodeficiency virus infection. N Engl J Med. 1989 Dec 14;321(24):1626–1631. doi: 10.1056/NEJM198912143212402. [DOI] [PubMed] [Google Scholar]
- Daniel M. D., Li Y., Naidu Y. M., Durda P. J., Schmidt D. K., Troup C. D., Silva D. P., MacKey J. J., Kestler H. W., 3rd, Sehgal P. K. Simian immunodeficiency virus from African green monkeys. J Virol. 1988 Nov;62(11):4123–4128. doi: 10.1128/jvi.62.11.4123-4128.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Desrosiers R. C., Wyand M. S., Kodama T., Ringler D. J., Arthur L. O., Sehgal P. K., Letvin N. L., King N. W., Daniel M. D. Vaccine protection against simian immunodeficiency virus infection. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6353–6357. doi: 10.1073/pnas.86.16.6353. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fauci A. S. The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science. 1988 Feb 5;239(4840):617–622. doi: 10.1126/science.3277274. [DOI] [PubMed] [Google Scholar]
- Hartung S., Boller K., Cichutek K., Norley S. G., Kurth R. Quantitation of a lentivirus in its natural host: simian immunodeficiency virus in African green monkeys. J Virol. 1992 Apr;66(4):2143–2149. doi: 10.1128/jvi.66.4.2143-2149.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hartung S., Norley S. G., Ennen J., Cichutek K., Plesker R., Kurth R. Vaccine protection against SIVmac infection by high- but not low-dose whole inactivated virus immunogen. J Acquir Immune Defic Syndr. 1992;5(5):461–468. [PubMed] [Google Scholar]
- Ho D. D., Moudgil T., Alam M. Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. N Engl J Med. 1989 Dec 14;321(24):1621–1625. doi: 10.1056/NEJM198912143212401. [DOI] [PubMed] [Google Scholar]
- Kannagi M., Chalifoux L. V., Lord C. I., Letvin N. L. Suppression of simian immunodeficiency virus replication in vitro by CD8+ lymphocytes. J Immunol. 1988 Apr 1;140(7):2237–2242. [PubMed] [Google Scholar]
- Kikukawa R., Koyanagi Y., Harada S., Kobayashi N., Hatanaka M., Yamamoto N. Differential susceptibility to the acquired immunodeficiency syndrome retrovirus in cloned cells of human leukemic T-cell line Molt-4. J Virol. 1986 Mar;57(3):1159–1162. doi: 10.1128/jvi.57.3.1159-1162.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kraus G., Werner A., Baier M., Binniger D., Ferdinand F. J., Norley S., Kurth R. Isolation of human immunodeficiency virus-related simian immunodeficiency viruses from African green monkeys. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2892–2896. doi: 10.1073/pnas.86.8.2892. [DOI] [PMC free article] [PubMed] [Google Scholar]
- König H., Behr E., Löwer J., Kurth R. Azidothymidine triphosphate is an inhibitor of both human immunodeficiency virus type 1 reverse transcriptase and DNA polymerase gamma. Antimicrob Agents Chemother. 1989 Dec;33(12):2109–2114. doi: 10.1128/aac.33.12.2109. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Martin L. N., Gormus B. J., Bozelka B. E. Functional analysis of monkey lymphocyte subsets defined by OKT4 and OKT8 Monoclonal Antibodies. Cell Immunol. 1983 Apr 15;77(2):338–347. doi: 10.1016/0008-8749(83)90034-5. [DOI] [PubMed] [Google Scholar]
- Miltenyi S., Müller W., Weichel W., Radbruch A. High gradient magnetic cell separation with MACS. Cytometry. 1990;11(2):231–238. doi: 10.1002/cyto.990110203. [DOI] [PubMed] [Google Scholar]
- Norley S. G., Kraus G., Ennen J., Bonilla J., König H., Kurth R. Immunological studies of the basis for the apathogenicity of simian immunodeficiency virus from African green monkeys. Proc Natl Acad Sci U S A. 1990 Nov;87(22):9067–9071. doi: 10.1073/pnas.87.22.9067. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Norley S. G., Löwer J., Kurth R. Insufficient inactivation of HIV-1 in human cryo poor plasma by beta-propiolactone: results from a highly accurate virus detection method. Biologicals. 1993 Sep;21(3):251–258. doi: 10.1006/biol.1993.1082. [DOI] [PubMed] [Google Scholar]
- Ohta Y., Masuda T., Tsujimoto H., Ishikawa K., Kodama T., Morikawa S., Nakai M., Honjo S., Hayami M. Isolation of simian immunodeficiency virus from African green monkeys and seroepidemiologic survey of the virus in various non-human primates. Int J Cancer. 1988 Jan 15;41(1):115–122. doi: 10.1002/ijc.2910410121. [DOI] [PubMed] [Google Scholar]
- Simmonds P., Balfe P., Peutherer J. F., Ludlam C. A., Bishop J. O., Brown A. J. Human immunodeficiency virus-infected individuals contain provirus in small numbers of peripheral mononuclear cells and at low copy numbers. J Virol. 1990 Feb;64(2):864–872. doi: 10.1128/jvi.64.2.864-872.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsubota H., Lord C. I., Watkins D. I., Morimoto C., Letvin N. L. A cytotoxic T lymphocyte inhibits acquired immunodeficiency syndrome virus replication in peripheral blood lymphocytes. J Exp Med. 1989 Apr 1;169(4):1421–1434. doi: 10.1084/jem.169.4.1421. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walker C. M., Erickson A. L., Hsueh F. C., Levy J. A. Inhibition of human immunodeficiency virus replication in acutely infected CD4+ cells by CD8+ cells involves a noncytotoxic mechanism. J Virol. 1991 Nov;65(11):5921–5927. doi: 10.1128/jvi.65.11.5921-5927.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walker C. M., Levy J. A. A diffusible lymphokine produced by CD8+ T lymphocytes suppresses HIV replication. Immunology. 1989 Apr;66(4):628–630. [PMC free article] [PubMed] [Google Scholar]
- Walker C. M., Moody D. J., Stites D. P., Levy J. A. CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. Science. 1986 Dec 19;234(4783):1563–1566. doi: 10.1126/science.2431484. [DOI] [PubMed] [Google Scholar]
- Walker C. M., Thomson-Honnebier G. A., Hsueh F. C., Erickson A. L., Pan L. Z., Levy J. A. CD8+ T cells from HIV-1-infected individuals inhibit acute infection by human and primate immunodeficiency viruses. Cell Immunol. 1991 Oct 15;137(2):420–428. doi: 10.1016/0008-8749(91)90090-x. [DOI] [PubMed] [Google Scholar]