Cleavage of mitochondrial antiviral signaling protein in the liver of patients with chronic hepatitis C correlates with a reduced activation of the endogenous interferon system†

• DOI: 10.1002/hep.23426
• Publication Date: 2009-11-13T19:14:46Z
• Authors: Pantxika Bellecave; Magdalena Sarasin...; Olivier Donzé; Audrey Kennel; Jérôme Gouttenoire; Etienne Meylan; Luigi Terracciano; Jürg Tschopp; Christoph Sarrazin; Thomas Berg; Darius Moradpour; Markus H. Heim
• Keywords: Cleavage (geology)

Hepatitis C virus (HCV) infection induces the endogenous interferon (IFN) system in liver some but not all patients with chronic hepatitis (CHC). Patients a pre-activated IFN are less likely to respond current standard therapy pegylated IFN-α. Mitochondrial antiviral signaling protein (MAVS) is an important adaptor molecule signal transduction pathway that senses viral infections and transcriptionally activates IFN-β. The HCV NS3-4A protease can cleave thereby inactivate MAVS vitro, and, therefore, might be crucial determining activation status of infected patients. We analyzed biopsies from 129 CHC investigate whether cleaved vivo cleavage prevents induction system. Cleavage was detected 62 samples (48%) more extensive high load. by genotypes (GTs), efficiently GTs 2 3 than 1 4. IFN-induced Janus kinase (Jak)-signal transducer activator transcription (STAT) frequently activated MAVS, there significant inverse correlation between expression level IFN-stimulated genes IFI44L, Viperin, IFI27, USP18, STAT1. conclude pre-activation part regulated MAVS. (HEPATOLOGY 2010.)