Human immunodeficiency virus type 1 Vpr: functions and molecular interactions

Abstract

Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) is an accessory protein that interacts with a number of cellular and viral proteins. The functions of many of these interactions in the pathogenesis of HIV-1 have been identified. Deletion of the vpr gene reduces the virulence of HIV-1 dramatically, indicating the importance of this protein for the virus. This review describes the current findings on several established functions of HIV-1 Vpr and some possible roles proposed for this protein. Because Vpr exploits cellular proteins and pathways to influence the biology of HIV-1, understanding the functions of Vpr usually involves the study of cellular pathways. Several functions of Vpr are attributed to the virion-incorporated protein, but some of them are attributed to the expression of Vpr in HIV-1-infected cells. The structure of Vpr may be key to understanding the variety of its interactions. Due to the critical role of Vpr in HIV-1 pathogenicity, study of the interactions between Vpr and cellular proteins may help us to understand the mechanism(s) of HIV-1 pathogenicity.

Protein intrinsic disorder as a flexible armor and a weapon of HIV-1

“…Each function or interaction of Vpr was attributed to one or more of its regions [439]. For example, the N-terminal region determines the cytopathic effects induced by Vpr, and it is able to form ion channels in cell membranes [434,435].…”

“…Furthermore, the N-terminal region together, with the helical domains, is essential for stability and virion incorporation [440,441]. The C-terminal domain of Vpr is responsible for alterations in the cell cycle, including apoptosis, cell-cycle arrest, and defects in mitosis [439]. Nuclear transport of Vpr is determined by a region comprised of the helix III and the C-terminal domain [442].…”

“…Furthermore, the C-terminal region, including helix III, is involved in Vpr oligomerization, likely via a leucine-zipper type mechanism involving helix III [446]. On the other hand, the incorporation of Vpr into the HIV-1 virion depends on different regions of the protein [439].…”

Functions of Tat: the versatile protein of human immunodeficiency virus type 1

“…In vitro studies have shown that HIV-1 Tat is able to induce the intrinsic pathway of apoptosis in a number of human cell lines. The results of these studies suggest that Tat promotes apoptosis during HIV-1 infection (Giacca, 2005;Kim et al, 2003;Park et al, 2001) although other proteins of HIV-1 (Vpr and gp120) have also been shown to induce apoptosis (Ramalingam et al, 2008;Romani & Engelbrecht, 2009;Vashistha et al, 2009). Extracellular Tat, produced by adjacent infected macrophages, microglia or astrocytes, can interact with the low density lipoprotein receptor-related protein (LRP) on the surfaces of neurons to enter cells by endocytosis.…”

HIV-Screening Strategies for the Discovery of Novel HIV-Inhibitors

“…Viral proteins are known to compete with the host proteins, thus disrupting the normal host protein-protein interaction network. HIV-1 encodes the regulatory proteins, Tat and Rev, and four accessory proteins: viral infectivity factor (Vif), viral protein R (Vpr), viral protein U (Vpu) and negative factor (Nef) (Romani & Engelbrecht, 2009, Romani et al, 2010. The regulatory proteins are essential for virus replication by controlling HIV gene expression in host cells.…”