HIV-1 subtype A gag variability and epitope evolution
OBJECTIVE: The aim of this study was to examine the course of time-dependent evolution of HIV-1 subtype A on a global level, especially with respect to the dynamics of immunogenic HIV gag epitopes. METHODS: We used a total of 1,893 HIV-1 subtype A gag sequences representing a timeline from 1985 thro...
| Главные авторы: | , , , , |
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| Формат: | Journal article |
| Язык: | English |
| Опубликовано: |
Public Library of Science
2014
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| _version_ | 1826292337938006016 |
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| author | Abidi, S Kalish, M Abbas, F Rowland-Jones, S Ali, S |
| author_facet | Abidi, S Kalish, M Abbas, F Rowland-Jones, S Ali, S |
| author_sort | Abidi, S |
| collection | OXFORD |
| description | OBJECTIVE: The aim of this study was to examine the course of time-dependent evolution of HIV-1 subtype A on a global level, especially with respect to the dynamics of immunogenic HIV gag epitopes. METHODS: We used a total of 1,893 HIV-1 subtype A gag sequences representing a timeline from 1985 through 2010, and 19 different countries in Africa, Europe and Asia. The phylogenetic relationship of subtype A gag and its epidemic dynamics was analysed through a Maximum Likelihood tree and Bayesian Skyline plot, genomic variability was measured in terms of G → A substitutions and Shannon entropy, and the time-dependent evolution of HIV subtype A gag epitopes was examined. Finally, to confirm observations on globally reported HIV subtype A sequences, we analysed the gag epitope data from our Kenyan, Pakistani, and Afghan cohorts, where both cohort-specific gene epitope variability and HLA restriction profiles of gag epitopes were examined. RESULTS: The most recent common ancestor of the HIV subtype A epidemic was estimated to be 1956 ± 1. A period of exponential growth began about 1980 and lasted for approximately 7 years, stabilized for 15 years, declined for 2-3 years, then stabilized again from about 2004. During the course of evolution, a gradual increase in genomic variability was observed that peaked in 2005-2010. We observed that the number of point mutations and novel epitopes in gag also peaked concurrently during 2005-2010. CONCLUSION: It appears that as the HIV subtype A epidemic spread globally, changing population immunogenetic pressures may have played a role in steering immune-evolution of this subtype in new directions. This trend is apparent in the genomic variability and epitope diversity of HIV-1 subtype A gag sequences. |
| first_indexed | 2024-03-07T03:13:08Z |
| format | Journal article |
| id | oxford-uuid:b4e53de3-cdc0-4c05-871f-2d6903c6e0a3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:13:08Z |
| publishDate | 2014 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:b4e53de3-cdc0-4c05-871f-2d6903c6e0a32022-03-27T04:29:23ZHIV-1 subtype A gag variability and epitope evolutionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b4e53de3-cdc0-4c05-871f-2d6903c6e0a3EnglishSymplectic Elements at OxfordPublic Library of Science2014Abidi, SKalish, MAbbas, FRowland-Jones, SAli, SOBJECTIVE: The aim of this study was to examine the course of time-dependent evolution of HIV-1 subtype A on a global level, especially with respect to the dynamics of immunogenic HIV gag epitopes. METHODS: We used a total of 1,893 HIV-1 subtype A gag sequences representing a timeline from 1985 through 2010, and 19 different countries in Africa, Europe and Asia. The phylogenetic relationship of subtype A gag and its epidemic dynamics was analysed through a Maximum Likelihood tree and Bayesian Skyline plot, genomic variability was measured in terms of G → A substitutions and Shannon entropy, and the time-dependent evolution of HIV subtype A gag epitopes was examined. Finally, to confirm observations on globally reported HIV subtype A sequences, we analysed the gag epitope data from our Kenyan, Pakistani, and Afghan cohorts, where both cohort-specific gene epitope variability and HLA restriction profiles of gag epitopes were examined. RESULTS: The most recent common ancestor of the HIV subtype A epidemic was estimated to be 1956 ± 1. A period of exponential growth began about 1980 and lasted for approximately 7 years, stabilized for 15 years, declined for 2-3 years, then stabilized again from about 2004. During the course of evolution, a gradual increase in genomic variability was observed that peaked in 2005-2010. We observed that the number of point mutations and novel epitopes in gag also peaked concurrently during 2005-2010. CONCLUSION: It appears that as the HIV subtype A epidemic spread globally, changing population immunogenetic pressures may have played a role in steering immune-evolution of this subtype in new directions. This trend is apparent in the genomic variability and epitope diversity of HIV-1 subtype A gag sequences. |
| spellingShingle | Abidi, S Kalish, M Abbas, F Rowland-Jones, S Ali, S HIV-1 subtype A gag variability and epitope evolution |
| title | HIV-1 subtype A gag variability and epitope evolution |
| title_full | HIV-1 subtype A gag variability and epitope evolution |
| title_fullStr | HIV-1 subtype A gag variability and epitope evolution |
| title_full_unstemmed | HIV-1 subtype A gag variability and epitope evolution |
| title_short | HIV-1 subtype A gag variability and epitope evolution |
| title_sort | hiv 1 subtype a gag variability and epitope evolution |
| work_keys_str_mv | AT abidis hiv1subtypeagagvariabilityandepitopeevolution AT kalishm hiv1subtypeagagvariabilityandepitopeevolution AT abbasf hiv1subtypeagagvariabilityandepitopeevolution AT rowlandjoness hiv1subtypeagagvariabilityandepitopeevolution AT alis hiv1subtypeagagvariabilityandepitopeevolution |