Vpx
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| UniProt | P06939 | ||||||
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Vpxis a virion-associated protein encoded by human immunodeficiency virus type 2HIV-2and mostsimian immunodeficiency virus (SIV)strains, but that is absent fromHIV-1.[1]It is similar in structure to the proteinVprthat 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 bylentivirusesthat 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 cellsandmacrophages,that restrictsHIV-1replication by depleting the cytoplasmic pool ofdeoxynucleoside triphosphatesneeded for viralDNAproduction.[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 transcriptionin 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]
References
[edit]- ^Vicenzi E, Poli G (February 2013). "Novel factors interfering with human immunodeficiency virus-type 1 replication in vivo and in vitro".Tissue Antigens.81(2): 61–71.doi:10.1111/tan.12047.PMID23330719.
- ^abcdeFujita M, Nomaguchi M, Adachi A, Otsuka M (2012)."SAMHD1-Dependent and -Independent Functions of HIV-2/SIV Vpx Protein".Frontiers in Microbiology.3:297.doi:10.3389/fmicb.2012.00297.PMC3415948.PMID22908011.
- ^abLaguette N, Rahm N, Sobhian B, Chable-Bessia C, Münch J, Snoeck J, et al. (February 2012)."Evolutionary and functional analyses of the interaction between the myeloid restriction factor SAMHD1 and the lentiviral Vpx protein".Cell Host & Microbe.11(2): 205–17.doi:10.1016/j.chom.2012.01.007.PMC3595996.PMID22305291.
- ^Lahouassa H, Daddacha W, Hofmann H, Ayinde D, Logue EC, Dragin L, et al. (February 2012)."SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates".Nature Immunology.13(3): 223–228.doi:10.1038/ni.2236.PMC3771401.PMID22327569.
- ^Wu X, Conway JA, Kim J, Kappes JC (October 1994)."Localization of the Vpx packaging signal within the C terminus of the human immunodeficiency virus type 2 Gag precursor protein".Journal of Virology.68(10): 6161–9.doi:10.1128/JVI.68.10.6161-6169.1994.PMC237035.PMID8083957.
- ^Fujita M, Otsuka M, Miyoshi M, Khamsri B, Nomaguchi M, Adachi A (August 2008)."Vpx is critical for reverse transcription of the human immunodeficiency virus type 2 genome in macrophages".Journal of Virology.82(15): 7752–6.doi:10.1128/JVI.01003-07.PMC2493314.PMID18495778.
- ^abBouzar AB, Guiguen F, Morin T, Villet S, Fornazero C, Garnier C, et al. (April 2003). "Specific G2 arrest of caprine cells infected with a caprine arthritis encephalitis virus expressing vpr and vpx genes from simian immunodeficiency virus".Virology.309(1): 41–52.doi:10.1016/S0042-6822(03)00014-X.PMID12726725.