Longitudinal analysis of an HLA-B*51-restricted epitope in integrase reveals immune escape in early HIV-1 infection

Yager, Nicloe, Robinson, Nicola, Brown, Helen, Flanagan, Peter, Frater, John, Fidler, Sarah, Weber, Jonathan, Phillips, Rodney, Fisher, Martin and The SPARTAC Trial Investigators, (2013) Longitudinal analysis of an HLA-B*51-restricted epitope in integrase reveals immune escape in early HIV-1 infection. AIDS, 27 (3). pp. 313-323. ISSN 0269-9370

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Abstract

Objective: To fully define cytotoxic T-lymphocyte (CTL) escape variants of an HLA-B*51-restricted integrase epitope in early HIV-1 infection.

Design: Ninety-four longitudinally sampled acute/early HIV-1 subtype B-infected participants were assessed to determine HLA-B*51-restricted LPPVVAKEI (LI9) escape variants.

Methods: LI9 was sequenced at baseline and subsequent time points. Interferon-γ (IFNγ) ELISpot assays were performed using serial log dilutions of variant LI9 peptides to determine the cellular response and functional avidity.

Results: There is a significant association between HLA-B*51 expression and an evolving LI9 sequence from baseline to year 1 (P < 0.0001). We detected that the V32I and P30X polymorphisms emerged within HLA-B*51+ participants over time. Reversion of the P30S polymorphism was observed by year 1 in one HLA-B*51− participant. LPPIIAKEI and LPSIVAKEI had significantly lower functional avidity compared with LPPVVAKEI and so may be less well recognized by LI9-specific CTLs; a positive IFNγ response to IPSVVAKEI was rarely seen. Functional avidity to wild-type LI9 inversely correlated with viral load (R2 = 0.448, P = 0.0485).

Conclusion: Our results provide support for the role of HLA-B*51-restricted CTLs and functional avidity in the control of early HIV-1 infection

Item Type: Article
Additional Information: Martin Fisher is part of the SPARTAC Trial Investigators
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
Subjects: R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine > RA0643 Communicable diseases and public health > RA0644 Individual diseases or groups of diseases, A-Z > RA0644.A25 AIDS. HIV infections
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Depositing User: Ellen Thomas
Date Deposited: 18 Nov 2013 15:39
Last Modified: 18 Nov 2013 15:39
URI: http://sro.sussex.ac.uk/id/eprint/47065
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