Selective inhibition of HIV replication in primary macrophages but not T lymphocytes by macrophage-derived chemokine.
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.
Cota
M
M
AIDS Immunopathogenesis Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
Mengozzi
M
M
Vicenzi
E
E
Panina-Bordignon
P
P
Sinigaglia
F
F
Transidico
P
P
Sozzani
S
S
Mantovani
A
A
Poli
G
G
D000998:Antiviral Agents / Q000378:metabolism / Q000502:physiology*; D001483:Base Sequence; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism / Q000502:physiology*; D017931:DNA Primers; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000821:virology*; D013601:T-Lymphocytes / Q000821:virology*; D014779:Virus Replication
D000998:Antiviral Agents; D018925:Chemokines; D017931:DNA Primers