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- Title
HCV E1 influences the fitness landscape of E2 and may enhance escape from E2-specific antibodies.
- Authors
Zhang, Hang; Bull, Rowena A; Quadeer, Ahmed Abdul; McKay, Matthew R
- Abstract
The Hepatitis C virus (HCV) envelope glycoprotein E1 forms a non-covalent heterodimer with E2, the main target of neutralizing antibodies. How E1–E2 interactions influence viral fitness and contribute to resistance to E2-specific antibodies remain largely unknown. We investigate this problem using a combination of fitness landscape and evolutionary modeling. Our analysis indicates that E1 and E2 proteins collectively mediate viral fitness and suggests that fitness-compensating E1 mutations may accelerate escape from E2-targeting antibodies. Our analysis also identifies a set of E2-specific human monoclonal antibodies that are predicted to be especially resilient to escape via genetic variation in both E1 and E2, providing directions for robust HCV vaccine development.
- Subjects
HEPATITIS C virus; IMMUNOGLOBULINS; MONOCLONAL antibodies; VACCINE development; HETERODIMERS; PRECOCIOUS puberty
- Publication
Virus Evolution, 2023, Vol 9, Issue 2, p1
- ISSN
2057-1577
- Publication type
Article
- DOI
10.1093/ve/vead068