HLA-associated polymorphisms in the HIV-2 capsid highlight key differences between HIV-1 and HIV-2 immune adaptation
<p><b>Objective:</b> 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 immunoge...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Lippincott, Williams & Wilkins
2018
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| _version_ | 1826287082280058880 |
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| author | de Silva, T Leligdowicz, A Carlson, J Garcia-Knight, M Onyango, C Miller, N Yindom, L Hué, S Jaye, A Dong, T Cotten, M Rowland-Jones, S |
| author_facet | de Silva, T Leligdowicz, A Carlson, J Garcia-Knight, M Onyango, C Miller, N Yindom, L Hué, S Jaye, A Dong, T Cotten, M Rowland-Jones, S |
| author_sort | de Silva, T |
| collection | OXFORD |
| description | <p><b>Objective:</b> 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. </p><p><b>Design and methods:</b> Bioinformatic algorithms to identify sites under positive and negative selective pressure and a statistical model of evolution to identify <i>HLA</i>-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. </p><p><b>Results:</b> We identified greater purifying selection and less sites under positive selective pressure in HIV-2 compared to HIV-1. Five HIV-2 codons with <i>HLA</i>-associated polymorphisms were detected all within or around known or predicted CTL epitopes. One site was within the <i>HLA</i>-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. </p><p><b>Conclusions:</b> 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.</p> |
| first_indexed | 2024-03-07T01:53:17Z |
| format | Journal article |
| id | oxford-uuid:9adce5c1-c140-4ae7-90c7-07a2d6ead08d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:53:17Z |
| publishDate | 2018 |
| publisher | Lippincott, Williams & Wilkins |
| record_format | dspace |
| spelling | oxford-uuid:9adce5c1-c140-4ae7-90c7-07a2d6ead08d2022-03-27T00:24:21ZHLA-associated polymorphisms in the HIV-2 capsid highlight key differences between HIV-1 and HIV-2 immune adaptationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9adce5c1-c140-4ae7-90c7-07a2d6ead08dEnglishSymplectic Elements at OxfordLippincott, Williams & Wilkins2018de Silva, TLeligdowicz, ACarlson, JGarcia-Knight, MOnyango, CMiller, NYindom, LHué, SJaye, ADong, TCotten, MRowland-Jones, S <p><b>Objective:</b> 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. </p><p><b>Design and methods:</b> Bioinformatic algorithms to identify sites under positive and negative selective pressure and a statistical model of evolution to identify <i>HLA</i>-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. </p><p><b>Results:</b> We identified greater purifying selection and less sites under positive selective pressure in HIV-2 compared to HIV-1. Five HIV-2 codons with <i>HLA</i>-associated polymorphisms were detected all within or around known or predicted CTL epitopes. One site was within the <i>HLA</i>-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. </p><p><b>Conclusions:</b> 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.</p> |
| spellingShingle | de Silva, T Leligdowicz, A Carlson, J Garcia-Knight, M Onyango, C Miller, N Yindom, L Hué, S Jaye, A Dong, T Cotten, M Rowland-Jones, S HLA-associated polymorphisms in the HIV-2 capsid highlight key differences between HIV-1 and HIV-2 immune adaptation |
| title | HLA-associated polymorphisms in the HIV-2 capsid highlight key differences between HIV-1 and HIV-2 immune adaptation |
| title_full | HLA-associated polymorphisms in the HIV-2 capsid highlight key differences between HIV-1 and HIV-2 immune adaptation |
| title_fullStr | HLA-associated polymorphisms in the HIV-2 capsid highlight key differences between HIV-1 and HIV-2 immune adaptation |
| title_full_unstemmed | HLA-associated polymorphisms in the HIV-2 capsid highlight key differences between HIV-1 and HIV-2 immune adaptation |
| title_short | HLA-associated polymorphisms in the HIV-2 capsid highlight key differences between HIV-1 and HIV-2 immune adaptation |
| title_sort | hla associated polymorphisms in the hiv 2 capsid highlight key differences between hiv 1 and hiv 2 immune adaptation |
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