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1.A.42 The HIV Viral Protein R (Vpr) Family

The mechanisms and functions of viral channel proteins have been reviewed by Fischer and Hsu (2011) and Fischer et al. (2012). HIV, a member of the lentivirus subfamily of retroviruses, encodes 3 genes (gag, pol and env) found in all retroviruses as well as six accessory genes, one of which is vpr. Vpr is a 96 aa protein encoded by HIV1, HIV2 and simian immunodeficiency virus. It is produced late in the viral life cycle and packaged in the viral particle. It facilitates infection of macrophage and induces cell cycle arrest in G2. It localizes to the nucleus, can induce apoptosis of infected cells and forms ion channels in lipid bilayers. The 3-D structure of Vpr is known. The cationic C-terminal domain includes an amphipathic/hydrophobic helix (residues 55-83) which overlaps a leucine-rich region that contains a short leucine zipper-like motif. The C-terminal fragment (residues 52-96), but not the whole protein, can deliver DNA into several tissue culture lines. It complexes DNA, facilitates cell entry, allows escape from the endosome, and facilitates entry into the nucleus. The shortened active fragment adopts an α-helical conformation, condenses the DNA and is membranolytic, properties that are probably essential for DNA transfection. Vpr interacts with the mitochondrial ATP:ADP anitporter, Ant (Sabbah et al. 2006).

The transport reaction believed to be catalyzed by Vpr or a C-terminal peptide derived from Vpr is:

Condensed DNA (out) condensed DNA (in)

References associated with 1.A.42 family:

Coeytaux, E., D. Coulaud, E. Le Cam, O. Danos, and A. Kichler. (2003). The cationic amphipathic α-helix of HIV-1 viral protein R (Vpr) binds to nucleic acids, permeabilizes membranes, and efficiently transfects cells. J. Biol. Chem. 278: 18110-18116. 12639957
Fischer, W.B. and H.J. Hsu. (2011). Viral channel forming proteins - modeling the target. Biochim. Biophys. Acta. 1808: 561-571. 20546700
Fischer, W.B., Y.T. Wang, C. Schindler, and C.P. Chen. (2012). Mechanism of function of viral channel proteins and implications for drug development. Int Rev Cell Mol Biol 294: 259-321. 22364876
Sabbah, E.N., S. Druillennec, N. Morellet, S. Bouaziz, G. Kroemer, and B.P. Roques. (2006). Interaction between the HIV-1 protein Vpr and the adenine nucleotide translocator. Chem Biol Drug Des 67: 145-154. 16492162