Human immunodeficiency virus 1 favors the persistence of infection by activating macrophages through TNF

AbstractMacrophages play a major role in HIV-1 persistence. In the present paper, we demonstrate that the absence of apoptosis in HIV-1-infected primary human monocyte-differentiated macrophages (MDM) correlates with an increase in anti-apoptotic (Bcl-2 and Bcl-xL) and a decrease in pro-apoptotic (Bax and Bad) proteins. This is associated with macrophage activation as shown by tumor necrosis factor (TNF) production and NF-κB activation upon infection. TNF production was shown to be involved in the upregulation of Bcl-2 and Bcl-xL because this increase was abolished by an anti-TNF anti-serum or an inhibitor of TNF synthesis. In parallel, inhibition of TNF production induced an increase in the number of apoptotic cells. Furthermore, using an inhibitor of NF-κB activation, we demonstrated that TNF-induced upregulation of Bcl-xL and Bcl-2 occurs, respectively, through a NF-κB-dependent and an NF-κB-independent pathway