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Variations in Trim5α and Cyclophilin A genes among HIV-1 elite controllers and non controllers in Uganda: a laboratory-based cross-sectional study

BACKGROUND: Tripartite Motif Containing 5 alpha (TRIM5α), a restriction factor produced ubiquitously in cells and tissues of the body plays an important role in the immune response against HIV. TRIM5α targets the HIV capsid for proteosomal destruction. Cyclophilin A, an intracellular protein has als...

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Autores principales: Amanya, Sharon Bright, Nyiro, Brian, Waswa, Francis, Obura, Bonniface, Nakaziba, Rebecca, Nabulime, Eva, Katabazi, Ashaba Fred, Nabatanzi, Rose, Bayiyana, Alice, Mboowa, Gerald, Kayongo, Alex, Wayengera, Misaki, Sande, Obondo J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339491/
https://www.ncbi.nlm.nih.gov/pubmed/32631377
http://dx.doi.org/10.1186/s12977-020-00527-z
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author Amanya, Sharon Bright
Nyiro, Brian
Waswa, Francis
Obura, Bonniface
Nakaziba, Rebecca
Nabulime, Eva
Katabazi, Ashaba Fred
Nabatanzi, Rose
Bayiyana, Alice
Mboowa, Gerald
Kayongo, Alex
Wayengera, Misaki
Sande, Obondo J.
author_facet Amanya, Sharon Bright
Nyiro, Brian
Waswa, Francis
Obura, Bonniface
Nakaziba, Rebecca
Nabulime, Eva
Katabazi, Ashaba Fred
Nabatanzi, Rose
Bayiyana, Alice
Mboowa, Gerald
Kayongo, Alex
Wayengera, Misaki
Sande, Obondo J.
author_sort Amanya, Sharon Bright
collection PubMed
description BACKGROUND: Tripartite Motif Containing 5 alpha (TRIM5α), a restriction factor produced ubiquitously in cells and tissues of the body plays an important role in the immune response against HIV. TRIM5α targets the HIV capsid for proteosomal destruction. Cyclophilin A, an intracellular protein has also been reported to influence HIV infectivity in a cell-specific manner. Accordingly, variations in TRIM5α and Cyclophilin A genes have been documented to influence HIV-1 disease progression. However, these variations have not been documented among Elite controllers in Uganda and whether they play a role in viral suppression remains largely undocumented. Our study focused on identifying the variations in TRIM5α and Cyclophilin A genes among HIV-1 Elite controllers and non-controllers in Uganda. RESULTS: From the sequence analysis, the rs10838525 G > A mutation in exon 2 of TRIM5α was only found among elite controllers (30%) while the rs3824949 in the 5′UTR was seen among 25% of the non-controllers. In the Cyclophilin A promoter, rs6850 was seen among 62.5% of the non-controllers and only among 10% elite controllers. Furthermore, rs17860048 in the Cyclophillin A promoter was predominantly seen among elite controllers (30%) and 12.5% non-controllers. From gene expression analysis, we noted that the respective genes were generally elevated among elite controllers, however, this difference was not statistically significant (TRIM5α p = 0.6095; Cyclophilin A p = 0.6389). CONCLUSION: Variations in TRIM5α and Cyclophillin A promoter may influence HIV viral suppression. The rs10838525 SNP in TRIM5α may contribute to viral suppression among HIV-1 elite controllers. The rs6850 in the cyclophillin A gene may be responsible for HIV-1 rapid progression among HIV-1 non-controllers. These SNPs should be investigated mechanistically to determine their precise role in HIV-1 viral suppression.
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spelling pubmed-73394912020-07-09 Variations in Trim5α and Cyclophilin A genes among HIV-1 elite controllers and non controllers in Uganda: a laboratory-based cross-sectional study Amanya, Sharon Bright Nyiro, Brian Waswa, Francis Obura, Bonniface Nakaziba, Rebecca Nabulime, Eva Katabazi, Ashaba Fred Nabatanzi, Rose Bayiyana, Alice Mboowa, Gerald Kayongo, Alex Wayengera, Misaki Sande, Obondo J. Retrovirology Research BACKGROUND: Tripartite Motif Containing 5 alpha (TRIM5α), a restriction factor produced ubiquitously in cells and tissues of the body plays an important role in the immune response against HIV. TRIM5α targets the HIV capsid for proteosomal destruction. Cyclophilin A, an intracellular protein has also been reported to influence HIV infectivity in a cell-specific manner. Accordingly, variations in TRIM5α and Cyclophilin A genes have been documented to influence HIV-1 disease progression. However, these variations have not been documented among Elite controllers in Uganda and whether they play a role in viral suppression remains largely undocumented. Our study focused on identifying the variations in TRIM5α and Cyclophilin A genes among HIV-1 Elite controllers and non-controllers in Uganda. RESULTS: From the sequence analysis, the rs10838525 G > A mutation in exon 2 of TRIM5α was only found among elite controllers (30%) while the rs3824949 in the 5′UTR was seen among 25% of the non-controllers. In the Cyclophilin A promoter, rs6850 was seen among 62.5% of the non-controllers and only among 10% elite controllers. Furthermore, rs17860048 in the Cyclophillin A promoter was predominantly seen among elite controllers (30%) and 12.5% non-controllers. From gene expression analysis, we noted that the respective genes were generally elevated among elite controllers, however, this difference was not statistically significant (TRIM5α p = 0.6095; Cyclophilin A p = 0.6389). CONCLUSION: Variations in TRIM5α and Cyclophillin A promoter may influence HIV viral suppression. The rs10838525 SNP in TRIM5α may contribute to viral suppression among HIV-1 elite controllers. The rs6850 in the cyclophillin A gene may be responsible for HIV-1 rapid progression among HIV-1 non-controllers. These SNPs should be investigated mechanistically to determine their precise role in HIV-1 viral suppression. BioMed Central 2020-07-06 /pmc/articles/PMC7339491/ /pubmed/32631377 http://dx.doi.org/10.1186/s12977-020-00527-z Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Amanya, Sharon Bright
Nyiro, Brian
Waswa, Francis
Obura, Bonniface
Nakaziba, Rebecca
Nabulime, Eva
Katabazi, Ashaba Fred
Nabatanzi, Rose
Bayiyana, Alice
Mboowa, Gerald
Kayongo, Alex
Wayengera, Misaki
Sande, Obondo J.
Variations in Trim5α and Cyclophilin A genes among HIV-1 elite controllers and non controllers in Uganda: a laboratory-based cross-sectional study
title Variations in Trim5α and Cyclophilin A genes among HIV-1 elite controllers and non controllers in Uganda: a laboratory-based cross-sectional study
title_full Variations in Trim5α and Cyclophilin A genes among HIV-1 elite controllers and non controllers in Uganda: a laboratory-based cross-sectional study
title_fullStr Variations in Trim5α and Cyclophilin A genes among HIV-1 elite controllers and non controllers in Uganda: a laboratory-based cross-sectional study
title_full_unstemmed Variations in Trim5α and Cyclophilin A genes among HIV-1 elite controllers and non controllers in Uganda: a laboratory-based cross-sectional study
title_short Variations in Trim5α and Cyclophilin A genes among HIV-1 elite controllers and non controllers in Uganda: a laboratory-based cross-sectional study
title_sort variations in trim5α and cyclophilin a genes among hiv-1 elite controllers and non controllers in uganda: a laboratory-based cross-sectional study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339491/
https://www.ncbi.nlm.nih.gov/pubmed/32631377
http://dx.doi.org/10.1186/s12977-020-00527-z
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