CCR5 promoter activity correlates with HIV disease progression by regulating CCR5 cell surface expression and CD4 T cell apoptosis

Abstract CCR5 is the major co-receptor for HIV and polymorphisms in the CCR5 gene as well as promoter region that alter cell surface expression have been associated with disease progression. We determined the relationship between CCR5 promoter polymorphisms and CD4 decline and other immunopathologic...

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Autores principales:	Anjali Joshi, Erin B. Punke, Melina Sedano, Bethany Beauchamp, Rima Patel, Cassady Hossenlopp, Ogechika K. Alozie, Jayanta Gupta, Debabrata Mukherjee, Himanshu Garg
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d544ef3a989b499d8dde2a45dda0a0a2
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spelling	oai:doaj.org-article:d544ef3a989b499d8dde2a45dda0a0a22021-12-02T12:30:19ZCCR5 promoter activity correlates with HIV disease progression by regulating CCR5 cell surface expression and CD4 T cell apoptosis10.1038/s41598-017-00192-x2045-2322https://doaj.org/article/d544ef3a989b499d8dde2a45dda0a0a22017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00192-xhttps://doaj.org/toc/2045-2322Abstract CCR5 is the major co-receptor for HIV and polymorphisms in the CCR5 gene as well as promoter region that alter cell surface expression have been associated with disease progression. We determined the relationship between CCR5 promoter polymorphisms and CD4 decline and other immunopathological features like immune activation and CD4+ T cell apoptosis in HIV patients. CCR5 promoter haplotype HHC was significantly associated with higher CD4 counts in patients. The relative promoter activity (RPA) of each haplotype was determined in vitro and combined promoter activity based on both alleles (CRPA) was assigned to each patients. Interestingly, CCR5 CRPA correlated inversely with CD4 counts and CD4:CD8 ratio specifically in viremic patients. In normal individuals, the CRPA correlated with the number of CCR5+ CD4+ T cells in the peripheral blood suggesting an effect on CCR5 expression. In a subset of high viremic patients harboring R5 tropic HIV, there was a strong correlation between CCR5 CRPA and both CD4 counts and CD4 T cell apoptosis. Our study demonstrates that, CCR5 promoter polymorphisms correlate with CD4 T cell loss possibly by regulating CD4 T cell apoptosis in HIV patients. Furthermore, assigning CRPAs to each patient is a new method of translating genotype to phenotype.Anjali JoshiErin B. PunkeMelina SedanoBethany BeauchampRima PatelCassady HossenloppOgechika K. AlozieJayanta GuptaDebabrata MukherjeeHimanshu GargNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anjali Joshi Erin B. Punke Melina Sedano Bethany Beauchamp Rima Patel Cassady Hossenlopp Ogechika K. Alozie Jayanta Gupta Debabrata Mukherjee Himanshu Garg CCR5 promoter activity correlates with HIV disease progression by regulating CCR5 cell surface expression and CD4 T cell apoptosis
description	Abstract CCR5 is the major co-receptor for HIV and polymorphisms in the CCR5 gene as well as promoter region that alter cell surface expression have been associated with disease progression. We determined the relationship between CCR5 promoter polymorphisms and CD4 decline and other immunopathological features like immune activation and CD4+ T cell apoptosis in HIV patients. CCR5 promoter haplotype HHC was significantly associated with higher CD4 counts in patients. The relative promoter activity (RPA) of each haplotype was determined in vitro and combined promoter activity based on both alleles (CRPA) was assigned to each patients. Interestingly, CCR5 CRPA correlated inversely with CD4 counts and CD4:CD8 ratio specifically in viremic patients. In normal individuals, the CRPA correlated with the number of CCR5+ CD4+ T cells in the peripheral blood suggesting an effect on CCR5 expression. In a subset of high viremic patients harboring R5 tropic HIV, there was a strong correlation between CCR5 CRPA and both CD4 counts and CD4 T cell apoptosis. Our study demonstrates that, CCR5 promoter polymorphisms correlate with CD4 T cell loss possibly by regulating CD4 T cell apoptosis in HIV patients. Furthermore, assigning CRPAs to each patient is a new method of translating genotype to phenotype.
format	article
author	Anjali Joshi Erin B. Punke Melina Sedano Bethany Beauchamp Rima Patel Cassady Hossenlopp Ogechika K. Alozie Jayanta Gupta Debabrata Mukherjee Himanshu Garg
author_facet	Anjali Joshi Erin B. Punke Melina Sedano Bethany Beauchamp Rima Patel Cassady Hossenlopp Ogechika K. Alozie Jayanta Gupta Debabrata Mukherjee Himanshu Garg
author_sort	Anjali Joshi
title	CCR5 promoter activity correlates with HIV disease progression by regulating CCR5 cell surface expression and CD4 T cell apoptosis
title_short	CCR5 promoter activity correlates with HIV disease progression by regulating CCR5 cell surface expression and CD4 T cell apoptosis
title_full	CCR5 promoter activity correlates with HIV disease progression by regulating CCR5 cell surface expression and CD4 T cell apoptosis
title_fullStr	CCR5 promoter activity correlates with HIV disease progression by regulating CCR5 cell surface expression and CD4 T cell apoptosis
title_full_unstemmed	CCR5 promoter activity correlates with HIV disease progression by regulating CCR5 cell surface expression and CD4 T cell apoptosis
title_sort	ccr5 promoter activity correlates with hiv disease progression by regulating ccr5 cell surface expression and cd4 t cell apoptosis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d544ef3a989b499d8dde2a45dda0a0a2
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CCR5 promoter activity correlates with HIV disease progression by regulating CCR5 cell surface expression and CD4 T cell apoptosis

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