[The mechanisms of hepatitis C virus resistance to interferon].
The aim of this review is to describe the role of hepatitis C proteins, non-structural protein 5A and envelope protein E2, in resistance to interferon alpha. These proteins contain interferon induced-protein kinase R binding domains. The binding renders the kinase inactive; therefore the phosphorylation of translation factor eIF2 is inhibited. The studies indicate that phosphorylation of eIF4E is also inhibited. As a result, with the sufficient pool of active eIF2 in infected cell, synthesis of viral proteins proceeds while cap- and cap binding factors-, among them eIF4E, -dependent synthesis of host proteins is diminished. It seems this process is one of the molecular mechanisms responsible for the resistance of hepatitis C virus to interferon, persistence in infected cell and the resultant difficulties in treatment of infected individuals.
Kmieciak
Dariusz
D
Department of Biochemistry and Molecular Biology, Karol Marcinkowski University of Medical Sciences, Swiecickiego 6 St., 60-781 Poznan, Poland. dkmiec@am.poznan.pl
D024882:Drug Resistance, Viral; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D016174:Hepacivirus / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*
D015852:Eukaryotic Initiation Factor-2; D039561:Eukaryotic Initiation Factor-4E; D016898:Interferon-alpha