Promoter Methylation of HIV Coreceptor-Related Genes CCR5 and CXCR4: Original Research

The persistence of human immunodeficiency virus (HIV) within viral reservoirs poses significant challenges to eradication efforts. Epigenetic alterations, including DNA methylation, are potential factors influencing the latency and persistence of HIV. This study details the development and applicati...

Full description

Saved in:
Bibliographic Details
Main Authors: Anna Esman, Svetlana Salamaikina, Alina Kirichenko, Michael Vinokurov, Darya Fomina, Kirill Sikamov, Arina Syrkina, Anastasia Pokrovskaya, Vasily Akimkin
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/17/4/465
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850180843861966848
author Anna Esman
Svetlana Salamaikina
Alina Kirichenko
Michael Vinokurov
Darya Fomina
Kirill Sikamov
Arina Syrkina
Anastasia Pokrovskaya
Vasily Akimkin
author_facet Anna Esman
Svetlana Salamaikina
Alina Kirichenko
Michael Vinokurov
Darya Fomina
Kirill Sikamov
Arina Syrkina
Anastasia Pokrovskaya
Vasily Akimkin
author_sort Anna Esman
collection DOAJ
description The persistence of human immunodeficiency virus (HIV) within viral reservoirs poses significant challenges to eradication efforts. Epigenetic alterations, including DNA methylation, are potential factors influencing the latency and persistence of HIV. This study details the development and application of techniques to assess CpG methylation in the promoter regions of the <i>CCR5</i> and <i>CXCR4</i> genes, which are key HIV-1 coreceptors. Using both Sanger sequencing and pyrosequencing methods, we examined 51 biological samples from 17 people living with HIV at three time points: baseline (week 0) and post-antiretroviral therapy (ART) at weeks 24 and 48. Our results revealed that <i>CXCR4</i> promoter CpG sites were largely unmethylated, while <i>CCR5</i> promoter CpGs exhibited significant variability in methylation levels. Specifically, <i>CCR5</i> CpG 1 showed a significant decrease in methylation from week 0 to week 48, while <i>CXCR4</i> CpG 3 displayed a significant decrease between week 0 and week 24. These differences were statistically significant when compared with non-HIV-infected controls. These findings demonstrate distinct methylation patterns between <i>CCR5</i> and <i>CXCR4</i> promoters in people living with HIV over time, suggesting that epigenetic modifications may play a role in regulating the persistence of HIV-1. Our techniques provide a reliable framework for assessing gene promoter methylation and could be applied in further research on the epigenetics of HIV.
format Article
id doaj-art-cfc8f258aa944babbd44788906ca789d
institution OA Journals
issn 1999-4915
language English
publishDate 2025-03-01
publisher MDPI AG
record_format Article
series Viruses
spelling doaj-art-cfc8f258aa944babbd44788906ca789d2025-08-20T02:18:01ZengMDPI AGViruses1999-49152025-03-0117446510.3390/v17040465Promoter Methylation of HIV Coreceptor-Related Genes CCR5 and CXCR4: Original ResearchAnna Esman0Svetlana Salamaikina1Alina Kirichenko2Michael Vinokurov3Darya Fomina4Kirill Sikamov5Arina Syrkina6Anastasia Pokrovskaya7Vasily Akimkin8Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Central Research Institute of Epidemiology, 111123 Moscow, RussiaFederal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Central Research Institute of Epidemiology, 111123 Moscow, RussiaFederal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Central Research Institute of Epidemiology, 111123 Moscow, RussiaFederal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Central Research Institute of Epidemiology, 111123 Moscow, RussiaFederal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Central Research Institute of Epidemiology, 111123 Moscow, RussiaFederal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Central Research Institute of Epidemiology, 111123 Moscow, RussiaFederal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Central Research Institute of Epidemiology, 111123 Moscow, RussiaFederal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Central Research Institute of Epidemiology, 111123 Moscow, RussiaFederal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Central Research Institute of Epidemiology, 111123 Moscow, RussiaThe persistence of human immunodeficiency virus (HIV) within viral reservoirs poses significant challenges to eradication efforts. Epigenetic alterations, including DNA methylation, are potential factors influencing the latency and persistence of HIV. This study details the development and application of techniques to assess CpG methylation in the promoter regions of the <i>CCR5</i> and <i>CXCR4</i> genes, which are key HIV-1 coreceptors. Using both Sanger sequencing and pyrosequencing methods, we examined 51 biological samples from 17 people living with HIV at three time points: baseline (week 0) and post-antiretroviral therapy (ART) at weeks 24 and 48. Our results revealed that <i>CXCR4</i> promoter CpG sites were largely unmethylated, while <i>CCR5</i> promoter CpGs exhibited significant variability in methylation levels. Specifically, <i>CCR5</i> CpG 1 showed a significant decrease in methylation from week 0 to week 48, while <i>CXCR4</i> CpG 3 displayed a significant decrease between week 0 and week 24. These differences were statistically significant when compared with non-HIV-infected controls. These findings demonstrate distinct methylation patterns between <i>CCR5</i> and <i>CXCR4</i> promoters in people living with HIV over time, suggesting that epigenetic modifications may play a role in regulating the persistence of HIV-1. Our techniques provide a reliable framework for assessing gene promoter methylation and could be applied in further research on the epigenetics of HIV.https://www.mdpi.com/1999-4915/17/4/465epigeneticHIV infectionsCpGmethylationHIV coreceptors<i>CCR5</i>
spellingShingle Anna Esman
Svetlana Salamaikina
Alina Kirichenko
Michael Vinokurov
Darya Fomina
Kirill Sikamov
Arina Syrkina
Anastasia Pokrovskaya
Vasily Akimkin
Promoter Methylation of HIV Coreceptor-Related Genes CCR5 and CXCR4: Original Research
Viruses
epigenetic
HIV infections
CpG
methylation
HIV coreceptors
<i>CCR5</i>
title Promoter Methylation of HIV Coreceptor-Related Genes CCR5 and CXCR4: Original Research
title_full Promoter Methylation of HIV Coreceptor-Related Genes CCR5 and CXCR4: Original Research
title_fullStr Promoter Methylation of HIV Coreceptor-Related Genes CCR5 and CXCR4: Original Research
title_full_unstemmed Promoter Methylation of HIV Coreceptor-Related Genes CCR5 and CXCR4: Original Research
title_short Promoter Methylation of HIV Coreceptor-Related Genes CCR5 and CXCR4: Original Research
title_sort promoter methylation of hiv coreceptor related genes ccr5 and cxcr4 original research
topic epigenetic
HIV infections
CpG
methylation
HIV coreceptors
<i>CCR5</i>
url https://www.mdpi.com/1999-4915/17/4/465
work_keys_str_mv AT annaesman promotermethylationofhivcoreceptorrelatedgenesccr5andcxcr4originalresearch
AT svetlanasalamaikina promotermethylationofhivcoreceptorrelatedgenesccr5andcxcr4originalresearch
AT alinakirichenko promotermethylationofhivcoreceptorrelatedgenesccr5andcxcr4originalresearch
AT michaelvinokurov promotermethylationofhivcoreceptorrelatedgenesccr5andcxcr4originalresearch
AT daryafomina promotermethylationofhivcoreceptorrelatedgenesccr5andcxcr4originalresearch
AT kirillsikamov promotermethylationofhivcoreceptorrelatedgenesccr5andcxcr4originalresearch
AT arinasyrkina promotermethylationofhivcoreceptorrelatedgenesccr5andcxcr4originalresearch
AT anastasiapokrovskaya promotermethylationofhivcoreceptorrelatedgenesccr5andcxcr4originalresearch
AT vasilyakimkin promotermethylationofhivcoreceptorrelatedgenesccr5andcxcr4originalresearch