Protein Vpx, HIV2 (Vpx)

Viral protein X (Vpx) is present in the viral particle and have been found to function in the early stage of viral replication. Vpx, on the other hand, is found only in HIV-2 and its ancestor simian immunodeficiency virus of sooty mangabeys (SIV/sm). This ∼13-kDa protein was found to confer virulence to the virus, the mechanism of which still remains largely unexplored. With a 22% similarity in amino acid sequence to HIV-2 Vpr, it was proposed that vpx came to exist as a gene duplication of vpr. Besides playing an important role in the nuclear import of viral DNA in dividing as well as nondividing cells, a cardinal function of HIV-2 Vpx is the induction of the proteolytic degradation of the triphosphohydrolase SAM domain- and HD domain-containing protein 1 (SAMHD1) through the E3 ubiquitin ligase complex in dendritic cells, macrophages, and monocytes. Being targeted for proteosomal degradation, depleted SAMHD1 augments HIV-2 infectivity by preventing the hydrolysis of intracellular deoxynucleoside triphosphates (dNTPs) necessary for the critical step of reverse transcription. More recently, Vpx was found to interact with and inhibit interferon regulatory factor (IRF), resulting in reduced mRNA levels and protein production of Toll-like receptor-dependent interleukin-6 (IL-6), IL-12p40, and tumor necrosis factor alpha (TNF-α). Amino acids 65 to 72 constitute the nuclear localization signal (NLS) of Vpx, and this region contains three crucial residues: K68, Y68, and R70. Alanine substitution of K68 and R70 abolishes the nuclear localization of the protein, and a substitution of K68 resulted in the inhibition of the ubiquitination of SAMHD1 as well as an impairment of reverse transcription.