Figure 1

The role of Vpr in HIV-1 infection and host permissiveness. 1). HIV-1 enters human cells via interaction with cell-surface receptors CD4 and co-receptors CXCR4 (T-cell tropic viruses) or CCR5 (macrophage tropic viruses). The virus fuses with the cell surface membrane introducing genetic material and virion proteins, which include gag proteins that comprise the matrix and nucleocapsid, the latter containing significant quantities of Vpr. 2). Vpr promotes the binding of the PIC (including MA, integrase (IN) and proviral DNA) to importins and nucleoporins, thereby facilitating nuclear entry of HIV-1 provirus into the nucleus of non-dividing cells. 3). Vpr binds to the p300/transcription factor initiation complex. This binding activity may recruit additional elements to the promoter, such as glucocorticoid receptor (GR). Alternatively, Vpr may bind to GR bound to GRE elements in the promoter to recruit the p300/TF complex. This results in both increased HIV-1 production, and the regulation of cellular genes that may increase viral permissiveness. 4). Vpr induces G₂ cell-cycle arrest by promoting phosphorylation of Chk1, which increases viral production. Interestingly, the biochemical properties that contribute to this effect may be important in HIV-1 production in cells that do not divide. This property is dependent on the degradation of an unknown factor, which is recruited to Vpr via DCAF-1 interaction. The factor(s) involved in G₂ arrest and viral permissiveness may be overlapping or unique. 5). HIV-1 buds from the cell, promoting further infection and pathogenesis.