de Silva, T. orcid.org/0000-0002-6498-9212, Leligdowicz, A., Carlson, J. et al. (9 more authors) (2018) HLA-associated polymorphisms in the HIV-2 capsid highlight key differences between HIV-1 and HIV-2 immune adaptation. AIDS, 32 (6). pp. 709-714. ISSN 0269-9370
Abstract
Objective: HIV-1 frequently adapts in response to immune pressure from cytotoxic T-lymphocytes (CTL). Many HIV-2 infected individuals have robust capsid-specific CTL responses associated with viral control. Despite this CTL pressure, adaptive changes in this key immunogenic HIV-2 protein have not previously been described. We sought to compare selective pressure on HIV-1 and HIV-2 capsids and identify HLA-associated viral polymorphisms in HIV-2.Design and methods:Bioinformatic algorithms to identify sites under positive and negative selective pressure and a statistical model of evolution to identify HLA-associated polymorphisms in HIV-2 was applied to sequences from a community cohort in Guinea-Bissau. IFN-γ ELISpots were used to compare T-cell responses to wild-type and variant epitopes.Results:We identified greater purifying selection and less sites under positive selective pressure in HIV-2 compared with HIV-1. Five HIV-2 codons with HLA-associated polymorphisms were detected all within or around known or predicted CTL epitopes. One site was within the HLA-B58 SuperType (ST)-restricted epitope (TSTVEEQIQW), the HIV-2 equivalent of the HIV-1 TW10 epitope. In contrast to HIV-1, where a T→N mutation at position 3 is associated with resulting loss of CTL control, an E→D mutation at position 5 was observed in HIV-2. Robust CTL responses to the variant HIV-2 epitope were seen, suggesting that HIV-2 adaptation may be at the level of T-cell receptor recognition.Conclusion:Greater constraints on evolution may exist in HIV-2, resulting in more purifying selection and different immune adaptation pathways in HIV-1 and HIV-2 capsids. This may allow CTL responses to persist in HIV-2.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018, The Authors. Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY) (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Cytotoxic T-lymphocyte; HIV-2; HLA |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 06 Mar 2019 16:32 |
Last Modified: | 07 Mar 2019 16:41 |
Published Version: | https://doi.org/10.1097/QAD.0000000000001753 |
Status: | Published |
Publisher: | Lippincott, Williams & Wilkins |
Refereed: | Yes |
Identification Number: | 10.1097/QAD.0000000000001753 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:141768 |