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World J Gastroenterol. Dec 21, 2013; 19(47): 8929-8939
Published online Dec 21, 2013. doi: 10.3748/wjg.v19.i47.8929
Post-translational modifications of hepatitis C viral proteins and their biological significance
Jana Hundt, Zhubing Li, Qiang Liu
Jana Hundt, Zhubing Li, Qiang Liu, Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada
Author contributions: Liu Q conceived the idea; Hundt J, Li Z and Liu Q wrote the paper. Hundt J and Li Z contributed equally to this article.
Supported by Canadian Institutes of Health Research, Saskatchewan Health Research Foundation, and Natural Sciences and Engineering Research Council of Canada
Correspondence to: Qiang Liu, PhD, Vaccine and Infectious Disease Organization-International Vaccine Center, University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK S7N 5E3, Canada.
Telephone: +1-306-9661567 Fax: +1-306-9667478
Received: September 17, 2013
Revised: November 10, 2013
Accepted: December 3, 2013
Published online: December 21, 2013

Replication of hepatitis C virus (HCV) depends on the interaction of viral proteins with various host cellular proteins and signalling pathways. Similar to cellular proteins, post-translational modifications (PTMs) of HCV proteins are essential for proper protein function and regulation, thus, directly affecting viral life cycle and the generation of infectious virus particles. Cleavage of the HCV polyprotein by cellular and viral proteases into more than 10 proteins represents an early protein modification step after translation of the HCV positive-stranded RNA genome. The key modifications include the regulated intramembranous proteolytic cleavage of core protein, disulfide bond formation of core, glycosylation of HCV envelope proteins E1 and E2, methylation of nonstructural protein 3 (NS3), biotinylation of NS4A, ubiquitination of NS5B and phosphorylation of core and NS5B. Other modifications like ubiquitination of core and palmitoylation of core and NS4B proteins have been reported as well. For some modifications such as phosphorylation of NS3 and NS5A and acetylation of NS3, we have limited understanding of their effects on HCV replication and pathogenesis while the impact of other modifications is far from clear. In this review, we summarize the available information on PTMs of HCV proteins and discuss their relevance to HCV replication and pathogenesis.

Keywords: Hepatitis C virus, Hepatitis C virus proteins, Post-translational modifications of proteins, Hepatitis C virus replication, Hepatitis C virus pathogenesis

Core tip: Post-translational modifications (PTMs) are an important step in protein maturation and associated with protein function, activity and/or protein life span. PTMs of viral proteins are often essential for regulation of processes involved in viral infections and can be crucial for infectious virion production. Moreover, identification of PTM sites in viral proteins is particularly useful for the development of antiviral drugs. This overview on PTMs of hepatitis C virus (HCV) proteins discusses how PTMs affect HCV replication and virus-induced pathogenesis.