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Journal of Virology logoLink to Journal of Virology
. 1990 Jul;64(7):3399–3406. doi: 10.1128/jvi.64.7.3399-3406.1990

Interference with human immunodeficiency virus (HIV) replication by CD8+ T cells in peripheral blood leukocytes of asymptomatic HIV carriers in vitro.

M Kannagi 1, T Masuda 1, T Hattori 1, T Kanoh 1, K Nasu 1, N Yamamoto 1, S Harada 1
PMCID: PMC249592  PMID: 1693704

Abstract

A long asymptomatic period is one of the characteristics of human immunodeficiency virus (HIV) infection, despite its fatal consequences. Antiviral defense in HIV-infected individuals controls viral replication during this period. In the present study, we demonstrate that peripheral blood leukocytes (PBL) of asymptomatic HIV-1 carriers, following exogenous HIV-1 infection in vitro, do not support viral replication. These cells do not produce detectable amounts of reverse transcriptase or accumulate unintegrated proviral DNA. This is a striking contrast to the behavior of HIV-1-infected PBL of seronegative individuals, which produce large amounts of RT and unintegrated DNA. Such resistance to HIV-1 replication is not seen in PBL of patients with advanced disease. Since the binding of HIV-1 to CD4 molecule is not impaired in PBL of asymptomatic carriers, the interference with HIV replication must occur after the stage of virus binding. PBL lose their resistance when CD8+ lymphocytes are removed. In addition, these PBL are not resistant to an exogenous infection with HIV-2. These observations suggest that certain populations of CD8+ lymphocytes of asymptomatic HIV-1 carriers operate on the target cells in PBL to block viral replication in an HIV-1-specific manner. Such CD8+ lymphocyte-mediated interference with HIV replication could play an important role in the maintenance of the period of disease latency.

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Selected References

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

  1. Anderson R. M., May R. M. Epidemiological parameters of HIV transmission. Nature. 1988 Jun 9;333(6173):514–519. doi: 10.1038/333514a0. [DOI] [PubMed] [Google Scholar]
  2. Aziz D. C., Hanna Z., Jolicoeur P. Severe immunodeficiency disease induced by a defective murine leukaemia virus. Nature. 1989 Apr 6;338(6215):505–508. doi: 10.1038/338505a0. [DOI] [PubMed] [Google Scholar]
  3. Bednarik D. P., Mosca J. D., Raj N. B., Pitha P. M. Inhibition of human immunodeficiency virus (HIV) replication by HIV-trans-activated alpha 2-interferon. Proc Natl Acad Sci U S A. 1989 Jul;86(13):4958–4962. doi: 10.1073/pnas.86.13.4958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bishop J. M. Retroviruses. Annu Rev Biochem. 1978;47:35–88. doi: 10.1146/annurev.bi.47.070178.000343. [DOI] [PubMed] [Google Scholar]
  5. Blumberg R. S., Paradis T., Hartshorn K. L., Vogt M., Ho D. D., Hirsch M. S., Leban J., Sato V. L., Schooley R. T. Antibody-dependent cell-mediated cytotoxicity against cells infected with the human immunodeficiency virus. J Infect Dis. 1987 Dec;156(6):878–884. doi: 10.1093/infdis/156.6.878. [DOI] [PubMed] [Google Scholar]
  6. Chinsky J., Soeiro R. Fv-1 host restriction of Friend leukemia virus: analysis of unintegrated proviral DNA. J Virol. 1981 Oct;40(1):45–55. doi: 10.1128/jvi.40.1.45-55.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Clavel F., Guétard D., Brun-Vézinet F., Chamaret S., Rey M. A., Santos-Ferreira M. O., Laurent A. G., Dauguet C., Katlama C., Rouzioux C. Isolation of a new human retrovirus from West African patients with AIDS. Science. 1986 Jul 18;233(4761):343–346. doi: 10.1126/science.2425430. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Harada S., Koyanagi Y., Yamamoto N. Infection of HTLV-III/LAV in HTLV-I-carrying cells MT-2 and MT-4 and application in a plaque assay. Science. 1985 Aug 9;229(4713):563–566. doi: 10.1126/science.2992081. [DOI] [PubMed] [Google Scholar]
  10. Hart C., Schochetman G., Spira T., Lifson A., Moore J., Galphin J., Sninsky J., Ou C. Y. Direct detection of HIV RNA expression in seropositive subjects. Lancet. 1988 Sep 10;2(8611):596–599. doi: 10.1016/s0140-6736(88)90639-3. [DOI] [PubMed] [Google Scholar]
  11. Hartley J. W., Fredrickson T. N., Yetter R. A., Makino M., Morse H. C., 3rd Retrovirus-induced murine acquired immunodeficiency syndrome: natural history of infection and differing susceptibility of inbred mouse strains. J Virol. 1989 Mar;63(3):1223–1231. doi: 10.1128/jvi.63.3.1223-1231.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Haseltine W. A. Replication and pathogenesis of the AIDS virus. J Acquir Immune Defic Syndr. 1988;1(3):217–240. [PubMed] [Google Scholar]
  13. Hildreth J. E., Orentas R. J. Involvement of a leukocyte adhesion receptor (LFA-1) in HIV-induced syncytium formation. Science. 1989 Jun 2;244(4908):1075–1078. doi: 10.1126/science.2543075. [DOI] [PubMed] [Google Scholar]
  14. Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967 Jun 14;26(2):365–369. doi: 10.1016/0022-2836(67)90307-5. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Hoxie J. A., Haggarty B. S., Bonser S. E., Rackowski J. L., Shan H., Kanki P. J. Biological characterization of a simian immunodeficiency virus-like retrovirus (HTLV-IV): evidence for CD4-associated molecules required for infection. J Virol. 1988 Aug;62(8):2557–2568. doi: 10.1128/jvi.62.8.2557-2568.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Kim S. Y., Byrn R., Groopman J., Baltimore D. Temporal aspects of DNA and RNA synthesis during human immunodeficiency virus infection: evidence for differential gene expression. J Virol. 1989 Sep;63(9):3708–3713. doi: 10.1128/jvi.63.9.3708-3713.1989. [DOI] [PMC free article] [PubMed] [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. Selective infection of human CD4+ cells by simian immunodeficiency virus: productive infection associated with envelope glycoprotein-induced fusion. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2443–2447. doi: 10.1073/pnas.86.7.2443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kozak C. A., Gromet N. J., Ikeda H., Buckler C. E. A unique sequence related to the ecotropic murine leukemia virus is associated with the Fv-4 resistance gene. Proc Natl Acad Sci U S A. 1984 Feb;81(3):834–837. doi: 10.1073/pnas.81.3.834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. 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]
  24. Lyerly H. K., Matthews T. J., Langlois A. J., Bolognesi D. P., Weinhold K. J. Human T-cell lymphotropic virus IIIB glycoprotein (gp120) bound to CD4 determinants on normal lymphocytes and expressed by infected cells serves as target for immune attack. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4601–4605. doi: 10.1073/pnas.84.13.4601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Maddon P. J., Dalgleish A. G., McDougal J. S., Clapham P. R., Weiss R. A., Axel R. The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell. 1986 Nov 7;47(3):333–348. doi: 10.1016/0092-8674(86)90590-8. [DOI] [PubMed] [Google Scholar]
  26. Ou C. Y., Kwok S., Mitchell S. W., Mack D. H., Sninsky J. J., Krebs J. W., Feorino P., Warfield D., Schochetman G. DNA amplification for direct detection of HIV-1 in DNA of peripheral blood mononuclear cells. Science. 1988 Jan 15;239(4837):295–297. doi: 10.1126/science.3336784. [DOI] [PubMed] [Google Scholar]
  27. Pedersen C., Nielsen C. M., Vestergaard B. F., Gerstoft J., Krogsgaard K., Nielsen J. O. Temporal relation of antigenaemia and loss of antibodies to core antigens to development of clinical disease in HIV infection. Br Med J (Clin Res Ed) 1987 Sep 5;295(6598):567–569. doi: 10.1136/bmj.295.6598.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Plata F., Autran B., Martins L. P., Wain-Hobson S., Raphaël M., Mayaud C., Denis M., Guillon J. M., Debré P. AIDS virus-specific cytotoxic T lymphocytes in lung disorders. Nature. 1987 Jul 23;328(6128):348–351. doi: 10.1038/328348a0. [DOI] [PubMed] [Google Scholar]
  29. Poli G., Orenstein J. M., Kinter A., Folks T. M., Fauci A. S. Interferon-alpha but not AZT suppresses HIV expression in chronically infected cell lines. Science. 1989 May 5;244(4904):575–577. doi: 10.1126/science.2470148. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Ratner L., Haseltine W., Patarca R., Livak K. J., Starcich B., Josephs S. F., Doran E. R., Rafalski J. A., Whitehorn E. A., Baumeister K. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985 Jan 24;313(6000):277–284. doi: 10.1038/313277a0. [DOI] [PubMed] [Google Scholar]
  32. Redfield R. R., Wright D. C., Tramont E. C. The Walter Reed staging classification for HTLV-III/LAV infection. N Engl J Med. 1986 Jan 9;314(2):131–132. doi: 10.1056/NEJM198601093140232. [DOI] [PubMed] [Google Scholar]
  33. Rook A. H., Lane H. C., Folks T., McCoy S., Alter H., Fauci A. S. Sera from HTLV-III/LAV antibody-positive individuals mediate antibody-dependent cellular cytotoxicity against HTLV-III/LAV-infected T cells. J Immunol. 1987 Feb 15;138(4):1064–1067. [PubMed] [Google Scholar]
  34. Schnittman S. M., Psallidopoulos M. C., Lane H. C., Thompson L., Baseler M., Massari F., Fox C. H., Salzman N. P., Fauci A. S. The reservoir for HIV-1 in human peripheral blood is a T cell that maintains expression of CD4. Science. 1989 Jul 21;245(4915):305–308. doi: 10.1126/science.2665081. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  37. Steck F. T., Rubin H. The mechanism of interference between an avian leukosis virus and Rous sarcoma virus. II. Early steps of infection by RSV of cells under conditions of interference. Virology. 1966 Aug;29(4):642–653. doi: 10.1016/0042-6822(66)90288-1. [DOI] [PubMed] [Google Scholar]
  38. Stevenson M., Meier C., Mann A. M., Chapman N., Wasiak A. Envelope glycoprotein of HIV induces interference and cytolysis resistance in CD4+ cells: mechanism for persistence in AIDS. Cell. 1988 May 6;53(3):483–496. doi: 10.1016/0092-8674(88)90168-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. Walker B. D., Chakrabarti S., Moss B., Paradis T. J., Flynn T., Durno A. G., Blumberg R. S., Kaplan J. C., Hirsch M. S., Schooley R. T. HIV-specific cytotoxic T lymphocytes in seropositive individuals. Nature. 1987 Jul 23;328(6128):345–348. doi: 10.1038/328345a0. [DOI] [PubMed] [Google Scholar]
  41. Walker B. D., Flexner C., Paradis T. J., Fuller T. C., Hirsch M. S., Schooley R. T., Moss B. HIV-1 reverse transcriptase is a target for cytotoxic T lymphocytes in infected individuals. Science. 1988 Apr 1;240(4848):64–66. doi: 10.1126/science.2451288. [DOI] [PubMed] [Google Scholar]
  42. Walker C. M., Moody D. J., Stites D. P., Levy J. A. CD8+ T lymphocyte control of HIV replication in cultured CD4+ cells varies among infected individuals. Cell Immunol. 1989 Apr 1;119(2):470–475. doi: 10.1016/0008-8749(89)90259-1. [DOI] [PubMed] [Google Scholar]
  43. 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]
  44. Watanabe M., Reimann K. A., DeLong P. A., Liu T., Fisher R. A., Letvin N. L. Effect of recombinant soluble CD4 in rhesus monkeys infected with simian immunodeficiency virus of macaques. Nature. 1989 Jan 19;337(6204):267–270. doi: 10.1038/337267a0. [DOI] [PubMed] [Google Scholar]
  45. Yarchoan R., Klecker R. W., Weinhold K. J., Markham P. D., Lyerly H. K., Durack D. T., Gelmann E., Lehrman S. N., Blum R. M., Barry D. W. Administration of 3'-azido-3'-deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex. Lancet. 1986 Mar 15;1(8481):575–580. doi: 10.1016/s0140-6736(86)92808-4. [DOI] [PubMed] [Google Scholar]

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