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Vpr

From Wikipedia, the free encyclopedia
Group of transport proteins
Protein family
VPR
solution structure of hiv-1 vpr (13-33) peptide in micells
Identifiers
SymbolVPR
PfamPF00522
InterProIPR000012
SCOP21dsk /SCOPe /SUPFAM
TCDB1.A.42
Available protein structures:
Pfam  structures /ECOD  
PDBRCSB PDB;PDBe;PDBj
PDBsumstructure summary

Vpr is aHuman immunodeficiency virus gene and protein product.[1][2] Vpr stands for "Viral Protein R". Vpr, a 96amino acid 14-kDa protein, plays an important role in regulating nuclear import of theHIV-1 pre-integration complex, and is required for virus replication and enhanced gene expression from provirus in dividing or non-dividing cells such as T cells or macrophages.[3] Vpr also inducesG2 cell cycle arrest and apoptosis in proliferating cells, which can result in immune dysfunction.[4][5]

Vpr is alsoimmunosuppressive due to its ability to sequester aproinflammatory transcriptional activator in the cytoplasm. HIV-2 contains both a Vpr protein and a related (bysequence homology)Vpx protein (Viral Protein X). Two functions of Vpr in HIV-1 are split between Vpr and Vpx inHIV-2, with the HIV-2 Vpr protein inducing cell cycle arrest and the Vpx protein required for nuclear import.

Vpr-binding protein

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Vpr-binding protein (VprBP) is a 1,507-amino-acid human protein that contains conserved domains, including YXXY repeats, theLis homology motif, andWD40 repeats.[6] VprBP acts as a substrate-recognition unit when associated with DNA damage-binding protein 1 (DDB1) as part of aCUL4–DDB1E3 ubiquitin ligase complex.[6] When bound to Vpr, VprBP allows Vpr to modulate the catalytic activity of the CUL4–DDB1 complex, inducing G2 cell cycle arrest in infected cells.[6]

VprBP also regulates p53-induced transcription and apoptotic pathways. p53 is an important tumor suppressor which induces either cell cycle arrest or apoptosis in response to DNA damage.[6]

In-vitro studies of Vpr

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The lack of an in vitro cell culture system that demonstrated a deficit in replication upon infection with viruses in the absence of Vpr has led to some mystery in the function of Vpr. Recently, there has been experiments on monocyte-derived dendritic cells (MDDCs) using a novel in-vitro infection system. These infected human dendritic cells showed a slower rate of replication when deprived of the Vpr protein in HIV-1 cells. This replication difference occurred in a single round of infection. This was shown to be due to decreased transcriptional output from the integrated HIV viral genome. Using mutational analysis (biochemical identification of mutational changes in a nucleotide sequence), prevention of cell cycle progression into mitosis was shown to be required for LTR-mediated viral expression. These findings suggest that the evolutionarily secured G2 cell cycle arrest function of Vpr (Viral Protein R) is essential for HIV-1 replication. Furthermore, this innovative in-vitro culture system will allow researchers to address mechanisms underlying Vpr-mediated enhancement of HIV-1 replication.[7]

References

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  1. ^Vpr+Gene+Products,+Human+Immunodeficiency+Virus at the U.S. National Library of MedicineMedical Subject Headings (MeSH)
  2. ^Genes,+Vpr at the U.S. National Library of MedicineMedical Subject Headings (MeSH)
  3. ^Bhardwaj V, Singh A, Choudhary A, Dalavi R, Ralte L, Chawngthu RL, et al. (September 2023)."HIV-1 Vpr induces ciTRAN to prevent transcriptional repression of the provirus".Science Advances.9 (36): eadh9170.doi:10.1126/sciadv.adh9170.PMC 10482341.PMID 37672576.
  4. ^Bukrinsky M, Adzhubei A (1999)."Viral protein R of HIV-1".Reviews in Medical Virology.9 (1):39–49.doi:10.1002/(SICI)1099-1654(199901/03)9:1<39::AID-RMV235>3.0.CO;2-3.PMID 10371671.
  5. ^Muthumani K, Choo AY, Zong WX, Madesh M, Hwang DS, Premkumar A, et al. (February 2006)."The HIV-1 Vpr and glucocorticoid receptor complex is a gain-of-function interaction that prevents the nuclear localization of PARP-1".Nature Cell Biology.8 (2):170–179.doi:10.1038/ncb1352.PMC 3142937.PMID 16429131.
  6. ^abcdKim K, Heo K, Choi J, Jackson S, Kim H, Xiong Y, An W (February 2012)."Vpr-binding protein antagonizes p53-mediated transcription via direct interaction with H3 tail".Molecular and Cellular Biology.32 (4):783–796.doi:10.1128/MCB.06037-11.PMC 3272969.PMID 22184063.
  7. ^Miller CM, Akiyama H, Agosto LM, Emery A, Ettinger CR, Swanstrom RI, et al. (July 2017)."Virion-Associated Vpr Alleviates a Postintegration Block to HIV-1 Infection of Dendritic Cells".Journal of Virology.91 (13).doi:10.1128/JVI.00051-17.PMC 5469257.PMID 28424288.
DNA
linear ds-DNA
(Duplodnaviria,
Varidnaviria)
Herpes simplex
VSPs:
capsid:
VNPs:
Vaccinia
VNPs:
Adenoviridae
VNPs:
circular ds-DNA
(Duplodnaviria,
Varidnaviria?)
Epstein–Barr
VSPs:
VNPs:
ncRNA:
Baculoviridae
VNPs:
other
(Riboviria,
Monodnaviria)
Polyomaviridae
(SV40,MPyV,MCPyV,HaPyV)
(non-enveloped circular ds-DNA)
VSPs:
capsid:
VNPs:
oncoprotein:
Hepatitis B
(circular partially ds-DNA)
VSPs:
VNPs:
RNA
ds-RNA
(Riboviria)
Rotavirus
(Duplornaviricota)
VNPs:
Rhinov.,Polio,Hep A,
etc. (Pisuviricota)
VNPs:
ss-RNA
positive-sense
(Riboviria)
Hepatitis C
(Kitrinoviricota)
VSPs:
VNPs:
SARS-CoV-2
(Pisuviricota)
VSPs:
VNPs:
ss-RNA
negative-sense
(Negarnaviricota)
Influenza virus
VSPs:
capsid:
glycoprotein:
VNPs:
Parainfluenza
VSPs:
glycoprotein:
Mumps
VSPs:
glycoprotein:
Measles
VSPs:
glycoprotein:
RSV
VSPs:
glycoprotein:
Zaire ebolavirus
VSPs:
capsid:
Indiana vesiculovirus
VSPs:
capsid:
RT
Structure and genome of HIV
VSPs:
VRAPs:
Multiple
Fusion protein
oncoprotein:
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