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

<jats:title>Abstract</jats:title> <jats:p>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 <jats:italic>tat</jats:italic>, <jats:italic>rev</jats:italic>, <jats:italic>nef</jats:italic>, <jats:italic>vif</jats:italic>, <jats:italic>vpr</jats:italic>, <jats:italic>vpx</jats:italic> and <jats:italic>vpu</jats:italic>. While the <jats:italic>tat</jats:italic> and <jats:italic>rev</jats:italic> genes encode regulatory proteins absolutely required for virus replication, <jats:italic>nef</jats:italic>, <jats:italic>vif</jats:italic>, <jats:italic>vpr, vpx</jats:italic> and <jats:italic>vpu</jats:italic> encode for small proteins referred to "auxiliary" (or "accessory"), since their expression is usually dispensable for virus growth in many <jats:italic>in vitro</jats:italic> systems. However, these auxiliary proteins are essential for viral replication and pathogenesis <jats:italic>in vivo</jats:italic>. The two <jats:italic>vpr</jats:italic>- and <jats:italic>vpx</jats:italic>-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 <jats:italic>vpr</jats:italic> gene. In this review, we will mainly focus on <jats:italic>vpr</jats:italic> from HIV-1 and discuss the most recent developments in our understanding of Vpr functions and its role during the virus replication cycle.</jats:p>