Work

In Vivo Determinants of Hepatitis C Virus Adaptation and Escape From Neutralizing Antibody AR5A

Year: 2025

Type: article

Abstract: BACKGROUND & AIMS: , to study adaptation and bNAb AR5A escape in the HCV-permissive human-liver chimeric mouse model. METHODS: with or without HVR1. The infection of human liver chimeric mice with these recombinants revealed adaptive mutations, and the potential mechanism of adaptation was extensively characterized in vitro. Finally, we tested the barrier to resistance of AR5A in vivo by challenging passively immunized animals with HVR1-deleted viruses, either with or without the AR5A escape substitution, L665S. RESULTS: , N430D and M702L substitutions increased both cell-free particle mediated infection and cell-to-cell spread, whereas N430D also increased thermal stability at 37°C. CONCLUSIONS: We show that L665S is an AR5A escape mutation in vivo, supporting the use of cost-effective vaccine escape studies in vitro. We also identify novel in vivo adaptive mutations and characterize their mechanism of action, thus facilitating interpretation of future HCV in vivo studies.

Source: Cellular and Molecular Gastroenterology and Hepatology

DOI: 10.1016/j.jcmgh.2025.101684