Vpu protein

Vpu
structure of the channel-forming trans-membrane domain of virus protein "u" (vpu) from HIV-1
Identifiers
SymbolVpu
PfamPF00558
InterProIPR008187
SCOP21vpu / SCOPe / SUPFAM
TCDB1.A.40
OPM superfamily262
OPM protein2k7y
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Viral Protein Unique
Identifiers
OrganismHIV-1
Symbolvpu
Entrez155945
RefSeq (Prot)NP_057855.1
UniProtP05919
Other data
Chromosomeviral genome: 0.01 - 0.01 Mb
Search for
StructuresSwiss-model
DomainsInterPro

Vpu is an accessory protein that in HIV is encoded by the vpu gene. Vpu stands for "Viral Protein U". The Vpu protein acts in the degradation of CD4 in the endoplasmic reticulum and in the enhancement of virion release from the plasma membrane of infected cells.[1] Vpu induces the degradation of the CD4 viral receptor and therefore participates in the general downregulation of CD4 expression during the course of HIV infection. Vpu-mediated CD4 degradation is thought to prevent CD4-Env binding in the endoplasmic reticulum to facilitate proper Env assembly into virions.[2] It is found in the membranes of infected cells, but not the virus particles themselves.

The Vpu gene is found exclusively in HIV-1 and some HIV-1-related simian immunodeficiency virus (SIV) isolates, such as SIVcpz, SIVgsn, and SIVmon, but not in HIV-2 or the majority of SIV isolates.[3] Structural similarities between Vpu and another small viral protein, M2, encoded by influenza A virus were first noted soon after the discovery of Vpu. Since then, Vpu has been shown to form cation-selective ion channels when expressed in Xenopus oocytes or mammalian cells and also when purified and reconstituted into planar lipid bilayers.[4] Vpu also permeabilizes membranes of bacteria and mammalian cells to small molecules.[5] Therefore, it is considered a member of the Viroporins family.[6]

  1. ^ Bour S, Schubert U, Strebel K (March 1995). "The human immunodeficiency virus type 1 Vpu protein specifically binds to the cytoplasmic domain of CD4: implications for the mechanism of degradation". Journal of Virology. 69 (3): 1510–20. doi:10.1128/JVI.69.3.1510-1520.1995. PMC 188742. PMID 7853484.
  2. ^ Estrabaud E, Le Rouzic E, Lopez-Vergès S, Morel M, Belaïdouni N, Benarous R, Transy C, Berlioz-Torrent C, Margottin-Goguet F (July 2007). "Regulated degradation of the HIV-1 Vpu protein through a betaTrCP-independent pathway limits the release of viral particles". PLOS Pathog. 3 (7): e104. doi:10.1371/journal.ppat.0030104. PMC 1933454. PMID 17676996.
  3. ^ Hussain A, Wesley C, Khalid M, Chaudhry A, Jameel S (January 2008). "Human immunodeficiency virus type 1 Vpu protein interacts with CD74 and modulates major histocompatibility complex class II presentation" (PDF). Journal of Virology. 82 (2): 893–902. doi:10.1128/JVI.01373-07. PMC 2224584. PMID 17959659.
  4. ^ Ewart GD, Sutherland T, Gage PW, Cox GB (October 1996). "The Vpu protein of human immunodeficiency virus type 1 forms cation-selective ion channels". Journal of Virology. 70 (10): 7108–15. doi:10.1128/JVI.70.10.7108-7115.1996. PMC 190763. PMID 8794357.
  5. ^ Gonzalez ME, Carrasco L (September 1998). "The human immunodeficiency virus type 1 Vpu protein enhances membrane permeability". Biochemistry. 37 (39): 13710–9. doi:10.1021/bi981527f. hdl:20.500.12105/7976. PMID 9753459.
  6. ^ Gonzalez ME, Carrasco L (Sep 2003). "Viroporins". FEBS Letters. 552 (1): 28–34. doi:10.1016/S0014-5793(03)00780-4. hdl:20.500.12105/7778. PMID 12972148. S2CID 209557930.