J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/03/805/12 $2.00
Volume 185, Number 5, March 3, 1997 805-816

C-C Chemokines Released by Lipopolysaccharide (LPS)-stimulated Human Macrophages Suppress HIV-1 Infection in Both Macrophages and T Cells

By Alessia Verani,^* Gabriella Scarlatti, Manola Comar, Eleonora Tresoldi, Simona Polo,^§ Mauro Giacca, Paolo Lusso,^§ Antonio G. Siccardi,^¶ and Donata Vercelli^*

From the ^* Molecular Immunoregulation,  Lymphocyte Differentiation, and ^§ Human Virology Unit, Department of Biological and Technological Research, San Raffaele Scientific Institute, 20132 Milan,  International Center for Genetic Engineering and Biotechnology, 34012 Trieste, and ^¶ Department of Biology and Genetics, University of Milan, 20100 Milan, Italy

Human immunodeficiency virus-1 (HIV-1) expression in monocyte-derived macrophages (MDM) infected in vitro is known to be inhibited by lipopolysaccharide (LPS). However, the mechanisms are incompletely understood. We show here that HIV-1 suppression is mediated by soluble factors released by MDM stimulated with physiologically significant concentrations of LPS. LPS-conditioned supernatants from MDM inhibited HIV-1 replication in both MDM and T cells. Depletion of C-C chemokines (RANTES, MIP-1, and MIP-1) neutralized the ability of LPS-conditioned supernatants to inhibit HIV-1 replication in MDM. A combination of recombinant C-C chemokines blocked HIV-1 infection as effectively as LPS. Here, we report an inhibitory effect of C-C chemokines on HIV replication 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 the infection by releasing factors that suppress HIV replication not only in monocytes but also in T lymphocytes.

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