Selective inhibition of HIV replication in primary macrophages but not T lymphocytes by macrophage-derived chemokine

^*AIDS Immunopathogenesis Unit, San Raffaele Scientific Institute, 20132 Milan, Italy; ^‡Roche Milano Ricerche, 20132 Milan, Italy; ^§Department of Immunology and Cell Biology, Mario Negri Institute, 20157 Milan, Italy; and ^¶Department of Biotechnology, University of Brescia, 25123 Brescia, Italy

Edited by Robert C. Gallo, Institute of Human Virology, Baltimore, MD, and approved June 2, 2000 (received for review August 23, 1999)

Abstract

Macrophage-derived chemokine (MDC) has been reported to inhibit different HIV-1 strains in activated peripheral blood mononuclear cells (T cell blasts), although other investigators have not confirmed these findings. Here we demonstrate that MDC inhibits the replication of CCR5-dependent (R5) HIV-1_BaL in monocyte-derived macrophages (MDM), but not in T cell blasts, although with variable potency depending on donor variability. Analysis of HIV-1_BaL proviral DNA synthesis in MDM indicated that the suppressive effect of MDC did not involve inhibition of early events such as entry or reverse transcription. Finally, an inverse correlation was observed between the levels of endogenous MDC secreted by uninfected MDM of different donors and the efficiency of different HIV strains, including two primary isolates with different coreceptor usage, to replicate in these cells. Thus, MDC represents an example of a chemokine inhibiting HIV replication in macrophages acting at one or more postentry levels in the virus life cycle.

Footnotes

↵ † M.C. and M.M. contributed equally to this work.
↵ ‖ To whom reprint requests should be addressed at: P2-P3 Laboratories, DIBIT, Via Olgettina n. 58, 20132, Milan, Italy. E-mail: poli.guido{at}hsr.it.
This paper was submitted directly (Track II) to the PNAS office.
Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.160359197.
Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.160359197
Abbreviations:

CB,

cord blood;

MDM,

monocyte-derived macrophages;

MDC,

macrophage-derived chemokine;

RANTES,

regulated upon activation normal T cell expressed and secreted;

MIP,

macrophage inflammatory protein;

MCP,

monocyte chemotactic protein;

RT,

reverse transcription;

Th,

T helper