HCV NS3 Blocking Effect on IFN Induced ISGs Like Viperin and IL28 With and Without NS4A

AuthorZahra Khanlarien
AuthorFarzaneh Sabahien
AuthorSeyed Younes Hosseinien
AuthorMostafa Ghaderien
Issued Date2014-06-01en
AbstractBackground: Hepatitis C virus (HCV) is able to down-regulate innate immune response. It is important to know the immune pathways that this virus interacts with. HCV non-structural protein 3 (NS3) plays an important role in this viral feature. HCV NS3 protein could affect the expression of antiviral protein such as viperin, and interleukin 28whichare important proteins in antiviral response. Objectives: HCV has developed different mechanisms to maintain a persistent infection, especially by disrupting type I interferon response and subsequent suppression of expression of Interferon stimulatory genes (ISGs). Viperin, a member of ISGs, is considered as a host antiviral protein, which interferes with viral replication. Since it is a good target for some viruses to evade host responses, it is interesting to study if HCV has evolved a mechanism to interfere with this member of ISGs. Materials and Methods: We evaluated the impact of NS3, NS3/4A and a mutated nonfunctional NS3 on ISGs expression such as viperin and IL-28 after the induction of IFN signaling Jak-STAT pathway using IFN-. Results: NS3 protein disrupted the expressions of viperin gene and IL-28, an inducer for the expression of ISGs and viperin itself. By comparing the roles of NS3 and NS3/4A protease activities in suppressing the innate immune responses, we also showed that NS3 (without NS4A) has the ability to down-regulate ISGs expression, similar to that of NS3/4A. Conclusions: ISGs expression is impeded by NS3 protease activity and its interaction with Jak-STAT pathway proteins. In addition, the NS3/4A substrates spectrum seems to be similar to those of NS3.en
DOIhttps://doi.org/10.5812/hepatmon.17822en
KeywordHepatitis Cen
KeywordNS3en
KeywordInterferon-Lambda Proteinen
PublisherBrieflandsen
TitleHCV NS3 Blocking Effect on IFN Induced ISGs Like Viperin and IL28 With and Without NS4Aen
TypeResearch Articleen

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