Inhibition of HIV type 1 BaL replication by MIP-1alpha, MIP-1beta, and RANTES in macrophages.
The beta-chemokines RANTES, MIP-1alpha, and MIP-1beta have been shown to inhibit the infection of T cells by macrophage-tropic HIV-1 strains by blocking env-driven HIV-1 fusion through competition for the chemokine receptors or receptor downregulation. This study was aimed at testing whether beta-chemokines also inhibit the productive infection of monocyte-derived macrophages (MDMs) by a monocytotropic HIV-1 strain, by using virus yield assays. The action of the beta-chemokines MIP-1alpha, MIP-1beta, and RANTES was captured with that of the alpha-chemokine interleukin 8 (IL-8) and of interferon alpha (IFN-alpha), which is a well-known broad-range inhibitor of viral replication. While IL-8 did not inhibit HIV-1 BaL replication in MDMs, the beta-chemokines were dose-dependently inhibitory. RANTES was the most effective, reaching at 300 ng/ml a protection similar to that obtained with IFN-alpha at 1000 IU/ml, and was even more inhibitory when added to MDMs after virus attachment. In contrast to IFN-alpha, the antiviral activity of beta-chemokines was restricted to HIV, because another virus was not inhibited. As compared with untreated MDMs, full-length proviral DNA at day 1 postinfection was inhibited in MDMs treated with RANTES either before or after the absorption phase, and even more so in IFN-treated MDMs, whereas in IL-8-treated MDMs no inhibition was observed. Our results indicate that in MDMs both RANTES and IFN affect early steps of HIV-1 BaL replication, preceding the completion of viral DNA synthesis.
Capobianchi
M R
MR
Institute of Virology, University La Sapienza, Rome, Italy.
Abbate
I
I
Antonelli
G
G
Turriziani
O
O
Dolei
A
A
Dianzani
F
F
D019380:Anti-HIV Agents / Q000494:pharmacology; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology*; D004279:DNA, Viral / Q000096:biosynthesis; D015658:HIV Infections / Q000517:prevention & control; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D008264:Macrophages / Q000821:virology*; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000378:metabolism; D013045:Species Specificity; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
D019380:Anti-HIV Agents; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D004279:DNA, Viral; D016898:Interferon-alpha; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D015215:Zidovudine