A Hepatitis C Virus Envelope Polymorphism Confers Resistance to Neutralization by Polyclonal Sera and Broadly Neutralizing Monoclonal Antibodies

Journal of Virology
Lisa N WasilewskiJustin R Bailey

Abstract

Hepatitis C virus (HCV) infection is a global health problem, with millions of chronically infected individuals at risk for cirrhosis and hepatocellular carcinoma. HCV vaccine development is vital in the effort toward disease control and eradication, an undertaking aided by an increased understanding of the mechanisms of resistance to broadly neutralizing antibodies (bNAbs). In this study, we identified HCV codons that vary deep in a phylogenetic tree of HCV sequences and showed that a polymorphism at one of these positions renders Bole1a, a computationally derived, ancestral genotype 1a HCV strain, resistant to neutralization by both polyclonal-HCV-infected plasma and multiple broadly neutralizing monoclonal antibodies with unique binding epitopes. This bNAb resistance mutation reduces replicative fitness, which may explain the persistence of both neutralization-sensitive and neutralization-resistant variants in circulating viral strains. This work identifies an important determinant of bNAb resistance in an ancestral, representative HCV genome, which may inform HCV vaccine development. Worldwide, more than 170 million people are infected with hepatitis C virus (HCV), the leading cause of hepatocellular carcinoma and liver tra...Continue Reading

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Citations

Sep 23, 2016·Current Opinion in Virology·Brian G PierceSteven Kh Foung
Jan 10, 2017·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Chaturaka RodrigoUNKNOWN InC(3) Study Group
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Dec 20, 2017·Proceedings of the National Academy of Sciences of the United States of America·Madeleine C MankowskiJustin R Bailey
Aug 14, 2018·The Journal of Infectious Diseases·Rodrigo Velázquez-MoctezumaJannick Prentoe
May 10, 2019·Journal of Virology·Michelle D ColbertJustin R Bailey
Aug 14, 2019·The Journal of Clinical Investigation·Valerie J KinchenJustin R Bailey
Aug 18, 2018·Frontiers in Immunology·Valerie J Kinchen, Justin R Bailey
Apr 4, 2021·Vaccines·Rodrigo Velázquez-MoctezumaJannick Prentoe
Jul 31, 2021·Current Opinion in Virology·Nicole FrumentoJustin R Bailey
Aug 18, 2021·Current Opinion in Virology·Elias H AugestadJannick Prentoe

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