C-C CHEMOKINES RELEASED BY LIPOPOLYSACCHARIDE (LPS)-STIMULATED HUMAN MACROPHAGES SUPPRESS HIV-1 INFECTION IN BOTH MACROPHAGES AND T-CELLS

Human immunodeficiency virus-1 (HIV-1) expression in monocyte-derived macrophages (MDM) infected in vitro is known to be inhibited by lipopo lysaccharide (LPS). However, the mechanisms are incompletely understoo d. We show here that HIV-1 suppression is mediated by soluble factors released by MDM stimulated with physiologically significant concentrat ions of LPS. LPS-conditioned supernatants from MDM inhibited HIV-1 rep lication in both MDM and T cells. Depletion of C-C chemokines (RANTES, MIP-1 alpha, and MIP-1 beta) neutralized the ability of LPS-condition ed supernatants to inhibit HIV-1 replication in MDM. A combination of recombinant C-C chemokines blocked HIV-1 infection as effectively as L PS. Here, we report an inhibitory effect of C-C chemokines on HIV repl ication in primary macrophages. Our results raise the possibility that monocytes may play a dual role in HIV infection: while representing a reservoir for the virus, they may contribute to the containment of th e infection by releasing factors that suppress HIV replication not onl y in monocytes but also in T lymphocytes.