The Vpr protein from HIV-1: distinct roles along the viral life cycle

Abstract

The genomes of human and simian immunodeficiency viruses (HIV and SIV) encode the gag, pol and env genes and contain at least six supplementary open reading frames termed tat, rev, nef, vif, vpr, vpx and vpu. While the tat and rev genes encode regulatory proteins absolutely required for virus replication, nef, vif, vpr, vpx and vpu encode for small proteins referred to "auxiliary" (or "accessory"), since their expression is usually dispensable for virus growth in many in vitro systems. However, these auxiliary proteins are essential for viral replication and pathogenesis in vivo. The two vpr- and vpx-related genes are found only in members of the HIV-2/SIVsm/SIVmac group, whereas primate lentiviruses from other lineages (HIV-1, SIVcpz, SIVagm, SIVmnd and SIVsyk) contain a single vpr gene. In this review, we will mainly focus on vpr from HIV-1 and discuss the most recent developments in our understanding of Vpr functions and its role during the virus replication cycle.

Figure 1

Schematic view of the early steps of the HIV-1 infection of a target cell. The functional events in which the Vpr protein is involved are highlighted. Vpr has been shown to play multiple functions during the virus life cycle, including an effect on the accuracy of the reverse-transcription process, the nuclear import of the viral DNA as a component of the pre-integration complex, cell cycle progression, regulation of apoptosis, and the transactivation of the HIV-LTR as well as host cell genes.

Figure 2

Three-dimensional structure of the HIV-1 Vpr protein (from [15]). The three α-helices (17–33, 38–50, 55–77) are colored in pink, blue and orange, respectively; the loops and flexible domains are in green. We can the Trp54 residue localized between the second and the third a-helix, and that is likely accessible for protein-protein interaction with UNG2 [54].