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 infection. 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 products of RT, but inhibited the synthesis of late RT products and strongly repressed nuclear import of the viral DNA, resulting in protection from infection. This effect was mediated by the CD14 receptor and involved activation of the p38 mitogen-activated protein kinase pathway. Disruption of this signaling pathway using a specific inhibitor of the p38 mitogen-activated protein kinase (SB203580) restored HIV-1 infection in the presence of LPS. These results suggest a novel view of the role of macrophage activation in anti-HIV responses of the immune system.
Zybarth
G
G
The Picower Institute for Medical Research, Manhasset, NY 11030, USA.
Reiling
N
N
Schmidtmayerova
H
H
Sherry
B
B
Bukrinsky
M
M
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004789:Enzyme Activation / Q000276:immunology; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000201:enzymology / Q000276:immunology* / Q000821:virology*; D020928:Mitogen-Activated Protein Kinases; D016662:Virus Integration / Q000276:immunology; D014779:Virus Replication / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases
D008070:Lipopolysaccharides; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D054303:HIV Reverse Transcriptase