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Updated: Jul 8, 2026

A Protocol for Analyzing Hepatitis C Virus Replication
Published on: June 26, 2014
Proteasome activator and antigen-processing aminopeptidases are regulated by virus-induced type I interferon in the
Eui-Cheol Shin1, Ulrike Seifert, Sabrina Urban
1Immunology Section, Liver Diseases Branch, NIDDK, National Institutes of Health, DHHS, Bethesda, MD 20892, USA.
Abstract:
Many components of the class I antigen-processing pathway are thought to be regulated solely by interferon-gamma (IFN-gamma). Herein, we report type I IFN-mediated induction of proteasome activator (PA28) subunits alpha and beta, endoplasmic reticulum aminopeptidase 1 (ERAP1), ERAP2, and leucine aminopeptidase (LAP). This mechanism was initiated by either synthetic RNA (poly(I-C)) or by hepatitis C virus (HCV) RNA-mediated induction of type I IFN and abrogated by blocking of type I IFN. In serial liver biopsies of chimpanzees with acute HCV infection, increases in PA28 subunit and aminopeptidase mRNA levels correlated with intrahepatic type I IFN responses and preceded intrahepatic IFN-gamma responses by several weeks. Thus, viral RNA-induced type I IFN regulates the antigen-processing machinery early during viral infection and prior to IFN-gamma response. This mechanism may contribute to the high effectiveness of type I IFN-based therapies if administered early during acute HCV infection.
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