title: HCV NS3 Blocking Effect on IFN Induced ISGs Like Viperin and IL28 With and Without NS4A.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors: Department of Medical Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IR Iran.
authors: Zahra
authors: Z
authors: Khanlari
authors: Department of Medical Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IR Iran.
authors: Farzaneh
authors: F
authors: Sabahi
authors: Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran.
authors: Seyed Younes
authors: SY
authors: Hosseini
authors: Department of Medical Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IR Iran.
authors: Mostafa
authors: M
authors: Ghaderi
keywords: Hepatitis C; Interferon-Lambda Protein; NS3