D
IPR002868

Hepatitis C virus, Non-structural 5a protein

InterPro entry
Short nameHCV_NS5a

Description

Although Hepatitis A virus, Hepatitis B virus, and Hepatitis C virus have similar names, because they all cause liver inflammation, these are distinctly different viruses both genetically and clinically. The Hepatitis C virus (HCV) is a small (50-80 nm in diameter), enveloped, single-stranded, positive sense RNA virus. It is member of the family Flaviviridae. There are seven genotypes and a number of subtypes with diverse geographic distributions. The genome of HCV consists of a single open reading frame. At the 5' and 3' ends of the RNA are the UTR regions that are not translated into proteins but are important to translation and replication of the viral RNA. The 5' UTR has a ribosome binding site (IRES - Internal ribosome entry site) that starts the translation of unique polyprotein that is later cut by cellular and viral proteases into 10 active structural and non-structural smaller proteins
[3]
.

This entry represents Non-structural 5a viral protein (NS5A). This zinc-containing phosphoprotein plays a role in the regulation of HCV RNA replication
[6, 5]
. Biochemical characterization of the complex formed by the interaction of NS5A-RNA show the importance of zinc in this interaction and confirm the binding of the protein to the viral genome
[7]
. The NS5a protein is phosphorylated when expressed in mammalian cells. It is thought to interact with the dsRNA-dependent (interferon inducible) kinase PKR,
P19525
[1, 2]
. It also modulates TNFRSF21/DR6 signaling pathway for viral propagation
[4]
.

References

1.Control of PKR protein kinase by hepatitis C virus nonstructural 5A protein: molecular mechanisms of kinase regulation. Gale M Jr, Blakely CM, Kwieciszewski B, Tan SL, Dossett M, Tang NM, Korth MJ, Polyak SJ, Gretch DR, Katze MG. Mol. Cell. Biol. 18, 5208-18, (1998). View articlePMID: 9710605

2.Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein. Gale MJ Jr, Korth MJ, Tang NM, Tan SL, Hopkins DA, Dever TE, Polyak SJ, Gretch DR, Katze MG. Virology 230, 217-27, (1997). View articlePMID: 9143277

3.Virology and cell biology of the hepatitis C virus life cycle: an update. Dubuisson J, Cosset FL. J Hepatol 61, S3-S13, (2014). PMID: 25443344

4.Hepatitis C Virus Exploits Death Receptor 6-mediated Signaling Pathway to Facilitate Viral Propagation. Luong TTD, Tran GVQ, Shin DJ, Lim YS, Hwang SB. Sci Rep 7, 6445, (2017). PMID: 28743875

5.Hepatitis C virus proteins: from structure to function. Moradpour D, Penin F. Curr Top Microbiol Immunol 369, 113-42, (2013). PMID: 23463199

6.The NS5A protein of hepatitis C virus is a zinc metalloprotein. Tellinghuisen TL, Marcotrigiano J, Gorbalenya AE, Rice CM. J Biol Chem 279, 48576-87, (2004). PMID: 15339921

7.Hepatitis C virus nonstructural protein 5A: biochemical characterization of a novel structural class of RNA-binding proteins. Hwang J, Huang L, Cordek DG, Vaughan R, Reynolds SL, Kihara G, Raney KD, Kao CC, Cameron CE. J Virol 84, 12480-91, (2010). PMID: 20926572

GO terms

Cross References

Contributing Member Database Entry
This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our Privacy Notice and Terms of Use.