Effect of cytokines on HIV replication in CD4+ lymphocytes: lack of identity with the CD8+ cell antiviral factor.
CD8+ cells from HIV-infected individuals inhibit HIV replication in cultured CD4+ cells by a nonlytic, non-MHC-restricted mechanism. The activity appears to be mediated in part by a soluble antiviral factor (CAF) secreted by the CD8+ cells. In an attempt to identify this factor a large panel of recombinant cytokines was examined for their effect on HIV replication in CD4+ cells. In addition to interferon-alpha and -beta, TNF alpha, TGF beta, and IL-8 reduced virus replication in a dose-dependent fashion. In some cases, the effect of the cytokine was also dependent on the HIV infection assay used to measure it. Antibodies against the inhibitory cytokines, as well as antibodies against TNF beta, IFN-alpha, IFN-beta, IL-4, and IL-6 did not inactivate the antiviral effect of CAF. The data suggest that CAF does not have identity with known antiviral cytokines and therefore CAF may be a novel antiviral factor.
Mackewicz
C E
CE
Cancer Research Institute, University of California, School of Medicine, San Francisco 94143-0128.
Ortega
H
H
Levy
J A
JA
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis; D000998:Antiviral Agents / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology*; D016827:CD8 Antigens; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D016176:T-Lymphocyte Subsets / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects* / Q000276:immunology*
D000998:Antiviral Agents; D016827:CD8 Antigens; D016207:Cytokines; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D015088:2',5'-Oligoadenylate Synthetase