Modulation of the type I interferon pathways by culture-adaptive hepatitis C virus core mutants

Abstract

Hepatitis C virus (HCV) often establishes a persistent infection that leads to chronic liver diseases. The viral core protein modulates various cellular activities involved in this process. We found two mutations, K23E and V31A, in the core gene of the transfected HCV JFH-1 genome, which had been replicated for a prolonged period. The mutant viruses escaped immunochemical detection by a core-specific antibody and demonstrated enhanced RNA replication and protein expression, compared to the parental virus. The mutant core proteins bound less tightly than the parental type core to the DEAD-box RNA helicase DDX3 and attenuated the TBK1-mediated activation of interferon-related promoters. These results suggest a mechanism by which the viruses adapt to attenuate cellular antiviral activity and to establish persistent infection. Structured summary of protein interactions: DDX3 and CORE colocalize by fluorescence microscopy (View Interaction: 1, 2, 3) DDX3 physically interacts with CORE by two hybrid (View Interaction: 1, 2, 3) CORE physically interacts with DDX3 by pull down (View Interaction: 1, 2, 3) (C) 2012 Published by Elsevier B. V. on behalf of the Federation of European Biochemical Societies.