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 proteins from related viruses are about 90 - 120 aas in length (encoded by HIV1, HIV2 and simian immunodeficiency virus). They are produced late in the viral life cycle and packaged in the viral particle. They facilitate infection of macrophage and induces cell cycle arrest in G2. They localize to the nucleus, can induce apoptosis of infected cells and form 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)