Activation-induced resistance of human macrophages to HIV-1 infection in vitro

Cells of the monocyte/macrophage lineage are the first targets of HIV-1 in patients and also serve as reservoirs for the virus during the course of in fection. We investigated the effects of cell activation on early events of HIV-1 infection of monocyte-derived macrophages. Addition of LPS, a potent stimulator of macrophages, at the time of infection stimulated entry of HIV -1 into monocyte-derived macrophages, as judged by accumulation of early pr oducts of RT, but inhibited the synthesis of late RT products and strongly repressed nuclear import of the viral DNA, resulting in protection from inf ection. This effect was mediated by the CD14 receptor and involved activati on of the p38 mitogen-activated protein kinase pathway. Disruption of this signaling pathway using a specific inhibitor of the p38 mitogen-activated p rotein kinase (SB203580) restored HIV-1 infection in the presence of LPS, T hese results suggest a novel view of the role of macrophage activation in a nti-HIV responses of the immune system.