Reduced CCR5 expression among Uganda HIV controllers
Abstract Background Several mechanisms including reduced CCR5 expression, protective HLA, viral restriction factors, broadly neutralizing antibodies, and more efficient T-cell responses, have been reported to account for HIV control among HIV controllers. However, no one mechanism universally accoun...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Retrovirology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12977-023-00626-7 |
| _version_ | 1797817800836775936 |
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| author | Brian Nyiro Sharon Bright Amanya Alice Bayiyana Francis Wasswa Eva Nabulime Alex Kayongo Immaculate Nankya Gerald Mboowa David Patrick Kateete Obondo James Sande |
| author_facet | Brian Nyiro Sharon Bright Amanya Alice Bayiyana Francis Wasswa Eva Nabulime Alex Kayongo Immaculate Nankya Gerald Mboowa David Patrick Kateete Obondo James Sande |
| author_sort | Brian Nyiro |
| collection | DOAJ |
| description | Abstract Background Several mechanisms including reduced CCR5 expression, protective HLA, viral restriction factors, broadly neutralizing antibodies, and more efficient T-cell responses, have been reported to account for HIV control among HIV controllers. However, no one mechanism universally accounts for HIV control among all controllers. In this study we determined whether reduced CCR5 expression accounts for HIV control among Ugandan HIV controllers. We determined CCR5 expression among Ugandan HIV controllers compared with treated HIV non-controllers through ex-vivo characterization of CD4 + T cells isolated from archived PBMCs collected from the two distinct groups. Results The percentage of CCR5 + CD4 + T cells was similar between HIV controllers and treated HIV non-controllers (ECs vs. NCs, P = 0.6010; VCs vs. NCs, P = 0.0702) but T cells from controllers had significantly reduced CCR5 expression on their cell surface (ECs vs. NCs, P = 0.0210; VCs vs. NCs, P = 0.0312). Furthermore, we identified rs1799987 SNP among a subset of HIV controllers, a mutation previously reported to reduce CCR5 expression. In stark contrast, we identified the rs41469351 SNP to be common among HIV non-controllers. This SNP has previously been shown to be associated with increased perinatal HIV transmission, vaginal shedding of HIV-infected cells and increased risk of death. Conclusion CCR5 has a non-redundant role in HIV control among Ugandan HIV controllers. HIV controllers maintain high CD4 + T cells despite being ART naïve partly because their CD4 + T cells have significantly reduced CCR5 densities. |
| first_indexed | 2024-03-13T08:59:54Z |
| format | Article |
| id | doaj.art-d404b6fb29e3407e8c1284220d7f36ce |
| institution | Directory Open Access Journal |
| issn | 1742-4690 |
| language | English |
| last_indexed | 2024-03-13T08:59:54Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Retrovirology |
| spelling | doaj.art-d404b6fb29e3407e8c1284220d7f36ce2023-05-28T11:26:31ZengBMCRetrovirology1742-46902023-05-012011710.1186/s12977-023-00626-7Reduced CCR5 expression among Uganda HIV controllersBrian Nyiro0Sharon Bright Amanya1Alice Bayiyana2Francis Wasswa3Eva Nabulime4Alex Kayongo5Immaculate Nankya6Gerald Mboowa7David Patrick Kateete8Obondo James Sande9New Jersey Medical School, Rutgers UniversityBaylor College of MedicineDepartment of Immunology and Molecular Biology, Makerere UniversityDepartment of Immunology and Molecular Biology, Makerere UniversityCentre for AIDS Research Laboratory, Joint Clinical Research CentreDepartment of Immunology and Molecular Biology, Makerere UniversityCentre for AIDS Research Laboratory, Joint Clinical Research CentreDepartment of Immunology and Molecular Biology, Makerere UniversityDepartment of Immunology and Molecular Biology, Makerere UniversityDepartment of Immunology and Molecular Biology, Makerere UniversityAbstract Background Several mechanisms including reduced CCR5 expression, protective HLA, viral restriction factors, broadly neutralizing antibodies, and more efficient T-cell responses, have been reported to account for HIV control among HIV controllers. However, no one mechanism universally accounts for HIV control among all controllers. In this study we determined whether reduced CCR5 expression accounts for HIV control among Ugandan HIV controllers. We determined CCR5 expression among Ugandan HIV controllers compared with treated HIV non-controllers through ex-vivo characterization of CD4 + T cells isolated from archived PBMCs collected from the two distinct groups. Results The percentage of CCR5 + CD4 + T cells was similar between HIV controllers and treated HIV non-controllers (ECs vs. NCs, P = 0.6010; VCs vs. NCs, P = 0.0702) but T cells from controllers had significantly reduced CCR5 expression on their cell surface (ECs vs. NCs, P = 0.0210; VCs vs. NCs, P = 0.0312). Furthermore, we identified rs1799987 SNP among a subset of HIV controllers, a mutation previously reported to reduce CCR5 expression. In stark contrast, we identified the rs41469351 SNP to be common among HIV non-controllers. This SNP has previously been shown to be associated with increased perinatal HIV transmission, vaginal shedding of HIV-infected cells and increased risk of death. Conclusion CCR5 has a non-redundant role in HIV control among Ugandan HIV controllers. HIV controllers maintain high CD4 + T cells despite being ART naïve partly because their CD4 + T cells have significantly reduced CCR5 densities.https://doi.org/10.1186/s12977-023-00626-7Elite controllersViremic controllersNon-controllersHIVCCR5 promoter polymorphisms |
| spellingShingle | Brian Nyiro Sharon Bright Amanya Alice Bayiyana Francis Wasswa Eva Nabulime Alex Kayongo Immaculate Nankya Gerald Mboowa David Patrick Kateete Obondo James Sande Reduced CCR5 expression among Uganda HIV controllers Retrovirology Elite controllers Viremic controllers Non-controllers HIV CCR5 promoter polymorphisms |
| title | Reduced CCR5 expression among Uganda HIV controllers |
| title_full | Reduced CCR5 expression among Uganda HIV controllers |
| title_fullStr | Reduced CCR5 expression among Uganda HIV controllers |
| title_full_unstemmed | Reduced CCR5 expression among Uganda HIV controllers |
| title_short | Reduced CCR5 expression among Uganda HIV controllers |
| title_sort | reduced ccr5 expression among uganda hiv controllers |
| topic | Elite controllers Viremic controllers Non-controllers HIV CCR5 promoter polymorphisms |
| url | https://doi.org/10.1186/s12977-023-00626-7 |
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