Angus, A.G.N., Loquet, A., Stack, S.J., Dalrymple, D., Gatherer, D., Penin, F. and Patel, A.H. (2012) Conserved glycine 33 residue in flexible domain I of hepatitis C virus core protein is critical for virus infectivity. Journal of Virology, 86(2), pp. 679-690. (doi: 10.1128/jvi.05452-11) (PMID:22072760) (PMCID:PMC3255827)
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Abstract
Hepatitis C virus core protein forms the viral nucleocapsid and plays a critical role in the formation of infectious particles. In this study, we demonstrate that the highly conserved residue G33, located within domain 1 of the core protein, is important for the production of cell culture-infectious virus (HCVcc). Alanine substitution at this position in the JFH1 genome did not alter viral RNA replication but reduced infectivity by ∼2 logs. Virus production by this core mutant could be rescued by compensatory mutations located immediately upstream and downstream of the original G33A mutation. The examination of the helix-loop-helix motif observed in the core protein structure (residues 15 to 41; Protein Data Bank entry 1CWX) indicated that the residues G33 and F24 are in close contact with each other, and that the G33A mutation induces a steric clash with F24. Molecular simulations revealed that the compensatory mutations increase the helix-loop-helix flexibility, allowing rescue of the core active conformation required for efficient virus production. Taken together, these data highlight the plasticity of core domain 1 conformation and illustrate the relationship between its structural tolerance to mutations and virus infectivity.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Gatherer, Dr Derek and Angus, Dr Allan and Patel, Professor Arvind |
Authors: | Angus, A.G.N., Loquet, A., Stack, S.J., Dalrymple, D., Gatherer, D., Penin, F., and Patel, A.H. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
Journal Name: | Journal of Virology |
Publisher: | American Society for Microbiology |
ISSN: | 0022-538X |
ISSN (Online): | 1098-5514 |
Published Online: | 09 November 2011 |
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