Figure 2.

A model of HIV-1 pathogenesis based on interactions between macrophages and T cells which account for increased immune suppression and cellular virion reservoirs. a) Viral glycoprotein gp120 activates the production of pro-inflammatory cytokines and chemokines by macrophages, attracting T cells in the vicinity of macrophages, thereby increasing the number of infected cells and fueling the viral reservoirs. HIV-1 proteins Nef, Tat, and Vpr activate the long terminal repeat (LTR) of HIV-1, resulting in sustained viral growth while also activating anti-apoptotic pathways that favor viral persistence and formation of viral reservoir. b) Viral protein Tat participates in CD4+ T cell death through TRAIL secretion by HIV-1 infected macrophages. Viral gp120 glycoproteins increase the expression of TNF and TNFR on macrophages and T cells, leading to CD8+ T cell apoptosis. Thus, macrophage signaling using viral proteins accounts for both viral persistence and immune suppression during HIV-1 infection.