Rare HLA drive additional HIV evolution compared to more frequent alleles.
HIV-1 can evolve HLA-specific escape variants in response to HLA-mediated cellular immunity. HLA alleles that are common in the host population may increase the frequency of such escape variants at the population level. When loss of viral fitness is caused by immune escape variation, these variants...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2009
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| _version_ | 1797103133437984768 |
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| author | Rousseau, C Lockhart, D Listgarten, J Maley, SN Kadie, C Learn, G Nickle, D Heckerman, D Deng, W Brander, C Ndung'u, T Coovadia, H Goulder, P Korber, B Walker, B Mullins, J |
| author_facet | Rousseau, C Lockhart, D Listgarten, J Maley, SN Kadie, C Learn, G Nickle, D Heckerman, D Deng, W Brander, C Ndung'u, T Coovadia, H Goulder, P Korber, B Walker, B Mullins, J |
| author_sort | Rousseau, C |
| collection | OXFORD |
| description | HIV-1 can evolve HLA-specific escape variants in response to HLA-mediated cellular immunity. HLA alleles that are common in the host population may increase the frequency of such escape variants at the population level. When loss of viral fitness is caused by immune escape variation, these variants may revert upon infection of a new host who does not have the corresponding HLA allele. Furthermore, additional escape variants may appear in response to the nonconcordant HLA alleles. Because individuals with rare HLA alleles are less likely to be infected by a partner with concordant HLA alleles, viral populations infecting hosts with rare HLA alleles may undergo a greater amount of evolution than those infecting hosts with common alleles due to the loss of preexisting escape variants followed by new immune escape. This hypothesis was evaluated using maximum likelihood phylogenetic trees of each gene from 272 full-length HIV-1 sequences. Recent viral evolution, as measured by the external branch length, was found to be inversely associated with HLA frequency in nef (p < 0.02), env (p < 0.03), and pol (p < or = 0.05), suggesting that rare HLA alleles provide a disproportionate force driving viral evolution compared to common alleles, likely due to the loss of preexisting escape variants during early stages postinfection. |
| first_indexed | 2024-03-07T06:15:46Z |
| format | Journal article |
| id | oxford-uuid:f10971b2-f734-416d-bff4-95fa39d2e7a7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:15:46Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:f10971b2-f734-416d-bff4-95fa39d2e7a72022-03-27T11:52:48ZRare HLA drive additional HIV evolution compared to more frequent alleles.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f10971b2-f734-416d-bff4-95fa39d2e7a7EnglishSymplectic Elements at Oxford2009Rousseau, CLockhart, DListgarten, JMaley, SNKadie, CLearn, GNickle, DHeckerman, DDeng, WBrander, CNdung'u, TCoovadia, HGoulder, PKorber, BWalker, BMullins, JHIV-1 can evolve HLA-specific escape variants in response to HLA-mediated cellular immunity. HLA alleles that are common in the host population may increase the frequency of such escape variants at the population level. When loss of viral fitness is caused by immune escape variation, these variants may revert upon infection of a new host who does not have the corresponding HLA allele. Furthermore, additional escape variants may appear in response to the nonconcordant HLA alleles. Because individuals with rare HLA alleles are less likely to be infected by a partner with concordant HLA alleles, viral populations infecting hosts with rare HLA alleles may undergo a greater amount of evolution than those infecting hosts with common alleles due to the loss of preexisting escape variants followed by new immune escape. This hypothesis was evaluated using maximum likelihood phylogenetic trees of each gene from 272 full-length HIV-1 sequences. Recent viral evolution, as measured by the external branch length, was found to be inversely associated with HLA frequency in nef (p < 0.02), env (p < 0.03), and pol (p < or = 0.05), suggesting that rare HLA alleles provide a disproportionate force driving viral evolution compared to common alleles, likely due to the loss of preexisting escape variants during early stages postinfection. |
| spellingShingle | Rousseau, C Lockhart, D Listgarten, J Maley, SN Kadie, C Learn, G Nickle, D Heckerman, D Deng, W Brander, C Ndung'u, T Coovadia, H Goulder, P Korber, B Walker, B Mullins, J Rare HLA drive additional HIV evolution compared to more frequent alleles. |
| title | Rare HLA drive additional HIV evolution compared to more frequent alleles. |
| title_full | Rare HLA drive additional HIV evolution compared to more frequent alleles. |
| title_fullStr | Rare HLA drive additional HIV evolution compared to more frequent alleles. |
| title_full_unstemmed | Rare HLA drive additional HIV evolution compared to more frequent alleles. |
| title_short | Rare HLA drive additional HIV evolution compared to more frequent alleles. |
| title_sort | rare hla drive additional hiv evolution compared to more frequent alleles |
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