Journal
AIDS
Volume 32, Issue 6, Pages 709-714Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0000000000001753
Keywords
cytotoxic T-lymphocyte; HIV-2; HLA
Categories
Funding
- Medical Research Council [MC_UU_12014/12, MC_UU_00008/11, G0801751, MC_U137884180, MC_U190085854, MC_UP_A900_1121, MR/L018942/1, G0600520, G1001046] Funding Source: Medline
- MRC [MC_U190085854, MC_UP_A900_1121, G1001046, MC_UU_00008/11, MR/L018942/1, MC_UU_12014/12, G0600520, G0801751] Funding Source: UKRI
Ask authors/readers for more resources
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-gamma 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. Copyright (C) 2018 The Author(s). Published by Wolters Kluwer Health, Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available