How hepatitis C virus counteracts the interferon response: the jury is still out on NS5A.
Interferons (IFNs) induce an antiviral state in the cell through complex and indirect mechanisms, which culminate in a direct inhibition of viral replication and stimulation of the host adaptive responses. Viruses often counteract with elaborate strategies to interfere with the induction as well as action of IFN effector molecules. This evolutionary battle between viruses and IFN components is a subject of intense research aimed at understanding the immunopathogenesis of viruses and the molecular basis of IFN signaling and action. In the case with hepatitis C virus (HCV), this may have profound implications for the therapeutic use of recombinant IFN in treating chronic hepatitis C. Depending on the subtype of HCV, current IFN-based treatment regimens are effective for only a small subset of chronic hepatitis C patients. Thus, one of the Holy Grails in HCV research is to understand the mechanisms by which the virus may evade IFN antiviral surveillance and establish persistent infection, which may eventually provide insights into new avenues for better antiviral therapy. Despite the lack of an efficient tissue culture system and an appropriate animal model for HCV infection, several mechanisms have been proposed based on clinical studies and in vitro experiments. This minireview focuses on the HCV NS5A nonstructural protein, which is implicated in playing a role in HCV tolerance to IFN treatment, possibly in part through its ability to inhibit the cellular IFN-induced PKR protein kinase.
Tan
S L
SL
Infectious Diseases Research, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. tan_seng-la@lilly.com
Katze
M G
MG
D000818:Animals; D016174:Hepacivirus / Q000276:immunology*; D006801:Humans; D007372:Interferons / Q000276:immunology*; D008954:Models, Biological; D015398:Signal Transduction; D015533:Transcriptional Activation; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000502:physiology*; D012324:RNA-Dependent RNA Polymerase
D007372:Interferons; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase