Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control
<p>Background</p> <p>HLA-B*35 is an HLA allele associated with rapid progression to AIDS. However, a mechanism underlying the detrimental effect of HLA-B*35 on disease outcome remains unknown. Recent studies demonstrated that most prevalent subtype HLA-B*35:01 is a detrimental alle...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Elsevier
2018
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| _version_ | 1826275761290477568 |
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| author | Murakoshi, H Koyanagi, M Akahoshi, T Chikata, T Kuse, N Gatanaga, H Rowland-Jones, S Oka, S Takiguchi, M |
| author_facet | Murakoshi, H Koyanagi, M Akahoshi, T Chikata, T Kuse, N Gatanaga, H Rowland-Jones, S Oka, S Takiguchi, M |
| author_sort | Murakoshi, H |
| collection | OXFORD |
| description | <p>Background</p> <p>HLA-B*35 is an HLA allele associated with rapid progression to AIDS. However, a mechanism underlying the detrimental effect of HLA-B*35 on disease outcome remains unknown. Recent studies demonstrated that most prevalent subtype HLA-B*35:01 is a detrimental allele in HIV-1 clade B-infected individuals. We here investigated the effect of mutations within the epitopes on HLA-B*35:01-restricted CD8+ T cells having abilities to suppress HIV-1 replication.</p> <p>Methods</p> <p>We analyzed 16 HLA-B*35:01-restricted epitope-specific T cells in 63 HIV-1 clade B-infected Japanese B*35:01+ individuals and identified HLA-B*35:01-restricted CD8+ T cells having abilities to suppress HIV-1 replication. We further analyzed the effect of HLA-associated mutations on the ability of these T cells.</p> <p>Findings</p> <p>The breadth of T cell responses to 4 epitopes was inversely associated with plasma viral load (pVL). However, the accumulation of an Y135F mutation in NefYF9 out of the 4 epitopes, which is selected by HLA-A*24:02-restricted T cells, affected the ability of YF9-specific T cells to suppress HIV-1 replication. HLA-B*35:01+ individuals harboring this mutation had much higher pVL than those without it. YF9-specific T cells failed to suppress replication of the Y135F mutant in vitro. These results indicate that this mutation impairs suppression of HIV-1 replication by YF9-specific T cells.</p> <p>Interpretation</p> <p>These findings indicate that the Y135F mutation is a key factor underlying the detrimental effect of HLA-B*35:01 on disease outcomes in HIV-1 clade B-infected individuals.</p> |
| first_indexed | 2024-03-06T23:03:42Z |
| format | Journal article |
| id | oxford-uuid:630e6bcd-e5ec-4528-a2bb-73a8397d31dc |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:03:42Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:630e6bcd-e5ec-4528-a2bb-73a8397d31dc2022-03-26T18:10:22ZImpact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 controlJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:630e6bcd-e5ec-4528-a2bb-73a8397d31dcEnglishSymplectic Elements at OxfordElsevier2018Murakoshi, HKoyanagi, MAkahoshi, TChikata, TKuse, NGatanaga, HRowland-Jones, SOka, STakiguchi, M<p>Background</p> <p>HLA-B*35 is an HLA allele associated with rapid progression to AIDS. However, a mechanism underlying the detrimental effect of HLA-B*35 on disease outcome remains unknown. Recent studies demonstrated that most prevalent subtype HLA-B*35:01 is a detrimental allele in HIV-1 clade B-infected individuals. We here investigated the effect of mutations within the epitopes on HLA-B*35:01-restricted CD8+ T cells having abilities to suppress HIV-1 replication.</p> <p>Methods</p> <p>We analyzed 16 HLA-B*35:01-restricted epitope-specific T cells in 63 HIV-1 clade B-infected Japanese B*35:01+ individuals and identified HLA-B*35:01-restricted CD8+ T cells having abilities to suppress HIV-1 replication. We further analyzed the effect of HLA-associated mutations on the ability of these T cells.</p> <p>Findings</p> <p>The breadth of T cell responses to 4 epitopes was inversely associated with plasma viral load (pVL). However, the accumulation of an Y135F mutation in NefYF9 out of the 4 epitopes, which is selected by HLA-A*24:02-restricted T cells, affected the ability of YF9-specific T cells to suppress HIV-1 replication. HLA-B*35:01+ individuals harboring this mutation had much higher pVL than those without it. YF9-specific T cells failed to suppress replication of the Y135F mutant in vitro. These results indicate that this mutation impairs suppression of HIV-1 replication by YF9-specific T cells.</p> <p>Interpretation</p> <p>These findings indicate that the Y135F mutation is a key factor underlying the detrimental effect of HLA-B*35:01 on disease outcomes in HIV-1 clade B-infected individuals.</p> |
| spellingShingle | Murakoshi, H Koyanagi, M Akahoshi, T Chikata, T Kuse, N Gatanaga, H Rowland-Jones, S Oka, S Takiguchi, M Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control |
| title | Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control |
| title_full | Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control |
| title_fullStr | Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control |
| title_full_unstemmed | Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control |
| title_short | Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control |
| title_sort | impact of a single hla a 24 02 associated escape mutation on the detrimental effect of hla b 35 01 in hiv 1 control |
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