Canine hepacivirus NS3 serine protease can cleave the human adaptor proteins MAVS and TRIF

Mariona Parera, Gloria Martrus, Sandra Franco, Bonaventura Clotet, Miguel Angel Martinez

Research output: Contribution to journalArticleResearchpeer-review

21 Citations (Scopus)

Abstract

Canine hepacivirus (CHV) was recently identified in domestic dogs and horses. The finding that CHV is genetically the virus most closely related to hepatitis C virus (HCV) has raised the question of whether HCV might have evolved as the result of close contact between dogs and/or horses and humans. The aim of this study was to investigate whether the NS3/4A serine protease of CHV specifically cleaves human mitochondrial antiviral signaling protein (MAVS) and Toll-IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF). The proteolytic activity of CHV NS3/4A was evaluated using a bacteriophage lambda genetic screen. Human MAVS- and TRIF-specific cleavage sites were engineered into the lambda cI repressor. Upon infection of Escherichia coli cells coexpressing these repressors and a CHV NS3/4A construct, lambda phage replicated up to 2000-fold more efficiently than in cells expressing a CHV protease variant carrying the inactivating substitution S139A. Comparable results were obtained when several HCV NS3/4A constructs of genotype 1b were assayed. This indicates that CHV can disrupt the human innate antiviral defense signaling pathway and suggests a possible evolutionary relationship between CHV and HCV. © 2012 Parera et al.
Original languageEnglish
Article numbere42481
JournalPLoS ONE
Volume7
Issue number8
DOIs
Publication statusPublished - 1 Aug 2012

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