Canine Hepacivirus NS3 Serine Protease Can Cleave the Human Adaptor Proteins MAVS and TRIF

摘要: 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 (HCV) has raised question of whether HCV might have evolved as result close contact between and/or horses humans. aim this study investigate NS3/4A serine protease specifically cleaves human mitochondrial antiviral signaling protein (MAVS) Toll-IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF). proteolytic activity evaluated using a bacteriophage lambda genetic screen. Human MAVS- TRIF-specific cleavage sites were engineered into cI repressor. Upon infection Escherichia coli cells coexpressing these repressors construct, phage replicated up 2000-fold more efficiently than expressing variant carrying inactivating substitution S139A. Comparable results obtained when several constructs genotype 1b assayed. This indicates can disrupt innate defense pathway suggests possible evolutionary relationship HCV.