Proteasome activator and antigen-processing aminopeptidases are regulated by virus-induced type I interferon in the hepatitis C virus-infected liver

Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
Eui-Cheol ShinBarbara Rehermann

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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Citations

Mar 24, 2009·Rheumatology International·Raquel RollínBenjamín Fernández-Gutiérrez
May 12, 2010·The Journal of Biological Chemistry·Stanley M Lemon
Feb 7, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Xin WeiXue-Fan Bai
Aug 1, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Tzu G WuWilliam Robert Fleischmann
Jul 16, 2013·Journal of the National Cancer Institute·Patrizia LeoneVito Racanelli
Sep 4, 2012·International Journal of Molecular Sciences·Loredana CifaldiDoriana Fruci
Mar 18, 2009·World Journal of Gastroenterology : WJG·Natalia A Osna
Jun 18, 2014·Frontiers in Immunology·Pil Soo SungEui-Cheol Shin
Jun 19, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sabrina UrbanUlrike Seifert
Mar 11, 2011·Cellular and Molecular Life Sciences : CMLS·Peter van Endert

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