The Hypervariable HIV-1 Capsid Protein Residues Comprise HLA-Driven CD8(+) T-Cell Escape Mutations and Covarying HLA-Independent Polymorphisms

Hayley Crawford; Philippa C. Matthews; Malinda Schaefer; Jonathan M. Carlson; Alasdair Leslie; William Kilembe; Susan Allen; Thumbi Ndung'u; David Heckerman; Eric Hunter; Philip J. R. Goulder

doi:10.1128/JVI.01879-10

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The Hypervariable HIV-1 Capsid Protein Residues Comprise HLA-Driven CD8(+) T-Cell Escape Mutations and Covarying HLA-Independent Polymorphisms

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The Hypervariable HIV-1 Capsid Protein Residues Comprise HLA-Driven CD8(+) T-Cell Escape Mutations and Covarying HLA-Independent Polymorphisms

Hayley Crawford, Philippa C. Matthews, Malinda Schaefer, Jonathan M. Carlson, Alasdair Leslie, William Kilembe, Susan Allen, Thumbi Ndung'u, David Heckerman, Eric Hunter, …

Journal of virology, Vol.85(3), pp.1384-1390

02/01/2011

DOI: 10.1128/JVI.01879-10

PMCID: PMC3020512

PMID: 21106744

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Abstract

One proposed HIV vaccine strategy is to induce Gag-specific CD8(+) T-cell responses that can corner the virus, through fitness cost of viral escape and unavailability of compensatory mutations. We show here that the most variable capsid residues principally comprise escape mutants driven by protective alleles HLA-B*57, -5801, and -8101 and covarying HLA-independent polymorphisms that arise in conjunction with these escape mutations. These covarying polymorphisms are potentially compensatory and are concentrated around three tropism-determining loops of p24, suggesting structural interdependencies. Our results demonstrate complex patterns of adaptation of HIV under immune selection pressure, the understanding of which should aid vaccine design.

Life Sciences & Biomedicine

Science & Technology

Virology

Details

Title: Subtitle: The Hypervariable HIV-1 Capsid Protein Residues Comprise HLA-Driven CD8(+) T-Cell Escape Mutations and Covarying HLA-Independent Polymorphisms
Creators: Hayley Crawford - University of Oxford
Philippa C. Matthews - Medawar Building for Pathogen Research
Malinda Schaefer - Emory University
Jonathan M. Carlson - Microsoft
Alasdair Leslie - Emory University
William Kilembe - Emory University
Susan Allen - Emory University
Thumbi Ndung'u - University of KwaZulu-Natal
David Heckerman - Microsoft
Eric Hunter - Emory University
Philip J. R. Goulder - University of Oxford
Resource Type: Journal article
Publication Details: Journal of virology, Vol.85(3), pp.1384-1390
Publisher: Amer Soc Microbiology
DOI: 10.1128/JVI.01879-10
PMID: 21106744
PMCID: PMC3020512
ISSN: 0022-538X
eISSN: 1098-5514
Number of pages: 7
Grant note: Wellcome Trust; European Commission International AIDS Vaccine Initiative R01AI064060 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) AI-46995; AI-64060 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Mark and Lisa Schwartz Foundation G0501777 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission G0501777 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC)
Language: English
Date published: 02/01/2011
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9984697043602771

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