HLA-associated polymorphisms in the HIV-2 capsid highlight key differences between HIV-1 and HIV-2 immune adaptation

Journal article

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 to 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.

Conclusions: 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.

Authors: de Silva, T; Leligdowicz, A; Carlson, J; Garcia-Knight, M; Onyango, C

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Lippincott, Williams & Wilkins
• Journal: AIDS
• Publication date: 2018-03-27
• Acceptance date: 2017-12-18
• DOI: 10.1097/qad.0000000000001753
• EISSN: 1473-5571
• ISSN: 0269-9370
• Pmid: 29369160
• Language: English
• Keywords: HIV-2; cytotoxic T-lymphocyte; HLA