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Conserved glycine 33 residue in flexible domain I of hepatitis C virus core protein is critical for virus infectivity

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Conserved glycine 33 residue in flexible domain I of hepatitis C virus core protein is critical for virus infectivity. / Angus, Allan G. N.; Loquet, Antoine; Stack, Séamus J. et al.

In: Journal of Virology, Vol. 86, No. 2, 01.2012, p. 679-690.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Angus, AGN, Loquet, A, Stack, SJ, Dalrymple, D, Gatherer, D, Penin, F & Patel, AH 2012, 'Conserved glycine 33 residue in flexible domain I of hepatitis C virus core protein is critical for virus infectivity', Journal of Virology, vol. 86, no. 2, pp. 679-690. https://doi.org/10.1128/JVI.05452-11

APA

Angus, A. G. N., Loquet, A., Stack, S. J., Dalrymple, D., Gatherer, D., Penin, F., & 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), 679-690. https://doi.org/10.1128/JVI.05452-11

Vancouver

Angus AGN, Loquet A, Stack SJ, Dalrymple D, Gatherer D, Penin F et al. Conserved glycine 33 residue in flexible domain I of hepatitis C virus core protein is critical for virus infectivity. Journal of Virology. 2012 Jan;86(2):679-690. doi: 10.1128/JVI.05452-11

Author

Angus, Allan G. N. ; Loquet, Antoine ; Stack, Séamus J. et al. / Conserved glycine 33 residue in flexible domain I of hepatitis C virus core protein is critical for virus infectivity. In: Journal of Virology. 2012 ; Vol. 86, No. 2. pp. 679-690.

Bibtex

@article{a5388caf275e406da887f8399523d777,
title = "Conserved glycine 33 residue in flexible domain I of hepatitis C virus core protein is critical for virus infectivity",
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.",
keywords = "Amino Acid Sequence, Cell Line, Conserved Sequence, Glycine, Hepacivirus, Hepatitis C, Humans, Molecular Sequence Data, Protein Structure, Tertiary, Sequence Alignment, Viral Core Proteins, Virus Replication",
author = "Angus, {Allan G. N.} and Antoine Loquet and Stack, {S{\'e}amus J.} and David Dalrymple and Derek Gatherer and Fran{\c c}ois Penin and Patel, {Arvind H.}",
year = "2012",
month = jan,
doi = "10.1128/JVI.05452-11",
language = "English",
volume = "86",
pages = "679--690",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "2",

}

RIS

TY - JOUR

T1 - Conserved glycine 33 residue in flexible domain I of hepatitis C virus core protein is critical for virus infectivity

AU - Angus, Allan G. N.

AU - Loquet, Antoine

AU - Stack, Séamus J.

AU - Dalrymple, David

AU - Gatherer, Derek

AU - Penin, François

AU - Patel, Arvind H.

PY - 2012/1

Y1 - 2012/1

N2 - 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.

AB - 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.

KW - Amino Acid Sequence

KW - Cell Line

KW - Conserved Sequence

KW - Glycine

KW - Hepacivirus

KW - Hepatitis C

KW - Humans

KW - Molecular Sequence Data

KW - Protein Structure, Tertiary

KW - Sequence Alignment

KW - Viral Core Proteins

KW - Virus Replication

U2 - 10.1128/JVI.05452-11

DO - 10.1128/JVI.05452-11

M3 - Journal article

C2 - 22072760

VL - 86

SP - 679

EP - 690

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 2

ER -