The role of SAMHD1 expression and its relation to HIV-2 (Vpx) gene production

Abstract

SAMHD1 (sterile alpha motif and HD domain 1) is a protein that is found in myeloid cells, which restricts HIV1 replication. It depletes the de-oxy-nucleoside tri-phosphate (dNTPs) pool needed for a viral cDNA synthesis leading to inhibition of viral replication inside the cells. However, it does not restrict HIV2 replication in myeloid cells due to the presence of viral Vpx protein. Vpx is a virion-associated protein which augments viral infectivity and it only exists in HIV2 and it has been recently shown in Simian Immunodeficiency Virus (SIV) and which can induce degradation of SAMHD1 protein. This increases the amount of dNTPs for viral reverse transcription in cytoplasm and HIV infection. HIV2 reverse transcription is believed to be less active than HIV1 and this could be the reason for the absence of Vpx from HIV1. Protein expression and interaction between Vpx and SAMHD1 remains unclear. The interaction of SAMHD1 and HIV2-VPx patients' cells can be considered as a first step to help in the development for more effective anti-HIV drugs and possible novel intervention therapy in the future. Present review article provides comprehensive insights on the above issue. We performed a comprehensive literature search in the bibliographic database "Pubmed," looking at studies discussing the SAMHDI and Vpx interactions.

Keywords: HIV-1; HIV-2; Macrophages; SAMHD1; Vpx protein.

Fig. 1

Structure of the human SAMHD1.

Fig. 2

Schematic representation of HIV1 and HIV2 genomes. Grey boxes represent structural genes; blue boxes indicate regulatory genes; and pink boxes indicate accessory genes. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

SAMHD1-dependent and -independent functions of Vpx..

Fig. 4

SAMHD1 restricts HIV-1 infection in resting CD4⁺ T-cells.