| Vpx | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Organism | Human immunodeficiency virus type 2 subtype A (isolate ROD) | ||||||
| Symbol | ? | ||||||
| UniProt | P06939 | ||||||
| |||||||
Vpx is a virion-associated protein encoded by human immunodeficiency virus type 2HIV-2 and mostsimian immunodeficiency virus (SIV) strains, but that is absent fromHIV-1.[1] It is similar in structure to the proteinVpr that is carried by SIV and HIV-2 as well as HIV-1.[2] Vpx is one of fiveaccessory proteins (Vif, Vpx,Vpr,Vpu, andNef) carried bylentiviruses that enhances viral replication by inhibiting host antiviral factors.[2]
Vpx enhances HIV-2 replication in humans by counteracting the host factorSAMHD1.[3] SAMHD1 is a host factor found in humanmyeloid cells, such asdendritic cells andmacrophages, that restrictsHIV-1 replication by depleting the cytoplasmic pool ofdeoxynucleoside triphosphates needed for viralDNA production.[4] SAMHD1 does not, however, restrict HIV-2 replication in myeloid cells due to the presence of viral Vpx. Vpx counteracts restriction by inducing the ubiquitin-proteasome-dependent degradation of SAMHD1.[3] Vpx-mediated degradation of SAMHD1 therefore decreases deoxynucleoside triphosphate hydrolysis, thereby increasing the availability of dNTPs for viralreverse transcription in thecytoplasm. It has been postulated that SAMHD1 degradation is required for HIV-2 replication because the HIV-2 reverse transcriptase (RT) is less active than the HIV-1 RT, which would be the reason for the absence of Vpx from HIV-1.[2] Because Vpx is required for HIV-2 reverse transcription and the early stages of theviral life cycle, it is packaged into virions in significant amounts.[5][6]
Vpx is also involved in the nuclear import of the HIV-2/SIV genomes and associated proteins,[7] but the specific mechanisms and interactions are currently unknown. Although Vpr and Vpx are similar in size (both are ~100 amino acids with 20-25% sequence similarity) and structure (both are predicted to have similar tertiary structure with three major helices), they serve very different roles in viral replication.[2] Vpx targets a host restriction factor for proteasomal degradation, while Vpr arrests the host cell cycle in the G2 phase.[2] However, they are both involved in the import of the viral preintegration complex into the host nucleus.[7]