Figure 1

HIV-1 proteins modulate signaling in the macrophage. The HIV-1 proteins Nef, Tat, Vpr, and gp120 alter cell signaling pathways, both in infected and uninfected macrophages. The presence of exogenous Nef, Tat and Vpr has been reported in sera of AIDS patients, which have the ability to enter the cells. HIV-1 proteins activate multiple transcription factors in macrophages including NF-κB, Sp-1 and AP-1, which have binding sites in the long terminal repeat (LTR) of HIV-1. The induction of these factors results in increased viral production. Furthermore, the activation of these transcription factors enhances cytokine production by macrophages primarily involved in AIDS pathogenesis. TNF promoter is shown as a prototype containing binding sites of NF-κB, Sp-1, and AP-1. Exogenous Nef and Vpr may enhance Tat-mediated transcription in addition to their effect on transcription factors. Moreover, the viral glycoprotein gp120 activates MAPK in uninfected and infected cells, resulting in increased TNFα production through ATF-2 binding sites of its promoter. Tat also stimulates CXCR4/CCR5 surface co-receptor expression, thus enhancing viral entry in cells. Besides LTR activation through transcription factors, Vpr-induced cell cycle arrest facilitates LTR stimulation.