1887

Abstract

Interleukin-10 (IL-10), a product of T lymphocytes, B cells and macrophages, participates in Th-2 immune responses and modulates macrophage functions including possible interactions with pathogens. We have found that Chinese hamster ovary cell-derived human recombinant (hr) IL-10 inhibits human immunodeficiency virus type 1 strains Ada and Ba-L (HIV-1 and HIV-l) replication in primary tissue culture- derived macrophages in a dose-dependent manner. Inhibition by IL-10 treatment (> 5 U/ml) was effective 72 h before or 24 h after infection and cytokine activity blocked by anti-hrIL-10 antibody (19F1), or lost after heat inactivation of IL-10. Viral production was measured by determining p24 and reverse transcriptase levels while reverse transcription kinetics for the long terminal repeat (LTR) and were assessed at timed intervals after infection and quantified by P endlabelling. IL-10 inhibited early steps of infection without modulating cell surface CD4 levels. The onset of LTR reverse transcription was delayed by 4 to 8 h and the number of LTR transcripts was decreased by 77% at 24 h and by 87 % 48 h after infection. IL-10 effects were reversible; after cytokine washout, cells treated before infection showed lower levels of virus compared with those treated after infection. IL-10 biological activity was confirmed in three virus-independent assays. These results demonstrate IL-10 decreases HIV-1 reverse transcription upon macrophage infection and subsequently mediates viral latency Therefore, IL-10 may be involved in the effective control of HIV-1-infected macrophages

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1994-12-01
2021-10-22
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