Inhibition of CXCR4-tropic HIV-1 infection by lipopolysaccharide: Evidence of different mechanisms in macrophages and T lymphocytes

Bacterial LPS protects primary human macrophages from infection by CCR5-tropic HIV-1 isolates through the release of the CC chemokines RANTES and macrophage inflammatory protein-1α and -1β. Here, we show that LPS also suppresses infection of macrophages by CXCR4-tropic HIV-1 isolates. A marked down-regulation of both CD4 and CXCR4 expression was associated with this effect. Furthermore, a soluble factor(s) released by macrophages upon LPS treatment inhibited infection with CXCR4-tropic HIV-1 isolate viruses in both macrophages and T lymphocytes. Infection of both cell types appeared to be blocked at the level of viral entry and was independent of stromal cell-derived factor-1, the only known natural ligand of CXCR4. Moreover, the suppressive effect of LPS was unrelated to the release of IFN-α and -β, macrophage-derived chemokine, leukemia inhibitory factor, or TNF-α. These results suggest the existence of potent HIV-1 inhibitory factor(s), uncharacterized to date, released by activated cells of the mononuclear phagocytic system.