Abrupt and altered cell-type specific DNA methylation profiles in blood during acute HIV infection persists despite prompt initiation of ART.
HIV-1 disrupts the host epigenetic landscape with consequences for disease pathogenesis, viral persistence, and HIV-associated comorbidities. Here, we examined how soon after infection HIV-associated epigenetic changes may occur in blood and whether early initiation of antiretroviral therapy (ART) i...
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2021
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oai:doaj.org-article:1d2a126202fa4f6dbc8e432b922308532021-12-02T20:00:24ZAbrupt and altered cell-type specific DNA methylation profiles in blood during acute HIV infection persists despite prompt initiation of ART.1553-73661553-737410.1371/journal.ppat.1009785https://doaj.org/article/1d2a126202fa4f6dbc8e432b922308532021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009785https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374HIV-1 disrupts the host epigenetic landscape with consequences for disease pathogenesis, viral persistence, and HIV-associated comorbidities. Here, we examined how soon after infection HIV-associated epigenetic changes may occur in blood and whether early initiation of antiretroviral therapy (ART) impacts epigenetic modifications. We profiled longitudinal genome-wide DNA methylation in monocytes and CD4+ T lymphocytes from 22 participants in the RV254/SEARCH010 acute HIV infection (AHI) cohort that diagnoses infection within weeks after estimated exposure and immediately initiates ART. We identified monocytes harbored 22,697 differentially methylated CpGs associated with AHI compared to 294 in CD4+ T lymphocytes. ART minimally restored less than 1% of these changes in monocytes and had no effect upon T cells. Monocyte DNA methylation patterns associated with viral load, CD4 count, CD4/CD8 ratio, and longitudinal clinical phenotypes. Our findings suggest HIV-1 rapidly embeds an epigenetic memory not mitigated by ART and support determining epigenetic signatures in precision HIV medicine. Trial Registration: NCT00782808 and NCT00796146.Michael J CorleyCarlo SacdalanAlina P S PangNitiya ChomcheyNisakorn RatnaratornVictor ValcourEugene KroonKyu S ChoAndrew C BeldenDonn ColbyMerlin RobbDenise HsuSerena SpudichRobert PaulSandhya VasanLishomwa C NdhlovuSEARCH010/RV254 and SEARCH013/RV304 study groupsPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 8, p e1009785 (2021) |
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Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
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Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Michael J Corley Carlo Sacdalan Alina P S Pang Nitiya Chomchey Nisakorn Ratnaratorn Victor Valcour Eugene Kroon Kyu S Cho Andrew C Belden Donn Colby Merlin Robb Denise Hsu Serena Spudich Robert Paul Sandhya Vasan Lishomwa C Ndhlovu SEARCH010/RV254 and SEARCH013/RV304 study groups Abrupt and altered cell-type specific DNA methylation profiles in blood during acute HIV infection persists despite prompt initiation of ART. |
| description |
HIV-1 disrupts the host epigenetic landscape with consequences for disease pathogenesis, viral persistence, and HIV-associated comorbidities. Here, we examined how soon after infection HIV-associated epigenetic changes may occur in blood and whether early initiation of antiretroviral therapy (ART) impacts epigenetic modifications. We profiled longitudinal genome-wide DNA methylation in monocytes and CD4+ T lymphocytes from 22 participants in the RV254/SEARCH010 acute HIV infection (AHI) cohort that diagnoses infection within weeks after estimated exposure and immediately initiates ART. We identified monocytes harbored 22,697 differentially methylated CpGs associated with AHI compared to 294 in CD4+ T lymphocytes. ART minimally restored less than 1% of these changes in monocytes and had no effect upon T cells. Monocyte DNA methylation patterns associated with viral load, CD4 count, CD4/CD8 ratio, and longitudinal clinical phenotypes. Our findings suggest HIV-1 rapidly embeds an epigenetic memory not mitigated by ART and support determining epigenetic signatures in precision HIV medicine. Trial Registration: NCT00782808 and NCT00796146. |
| format |
article |
| author |
Michael J Corley Carlo Sacdalan Alina P S Pang Nitiya Chomchey Nisakorn Ratnaratorn Victor Valcour Eugene Kroon Kyu S Cho Andrew C Belden Donn Colby Merlin Robb Denise Hsu Serena Spudich Robert Paul Sandhya Vasan Lishomwa C Ndhlovu SEARCH010/RV254 and SEARCH013/RV304 study groups |
| author_facet |
Michael J Corley Carlo Sacdalan Alina P S Pang Nitiya Chomchey Nisakorn Ratnaratorn Victor Valcour Eugene Kroon Kyu S Cho Andrew C Belden Donn Colby Merlin Robb Denise Hsu Serena Spudich Robert Paul Sandhya Vasan Lishomwa C Ndhlovu SEARCH010/RV254 and SEARCH013/RV304 study groups |
| author_sort |
Michael J Corley |
| title |
Abrupt and altered cell-type specific DNA methylation profiles in blood during acute HIV infection persists despite prompt initiation of ART. |
| title_short |
Abrupt and altered cell-type specific DNA methylation profiles in blood during acute HIV infection persists despite prompt initiation of ART. |
| title_full |
Abrupt and altered cell-type specific DNA methylation profiles in blood during acute HIV infection persists despite prompt initiation of ART. |
| title_fullStr |
Abrupt and altered cell-type specific DNA methylation profiles in blood during acute HIV infection persists despite prompt initiation of ART. |
| title_full_unstemmed |
Abrupt and altered cell-type specific DNA methylation profiles in blood during acute HIV infection persists despite prompt initiation of ART. |
| title_sort |
abrupt and altered cell-type specific dna methylation profiles in blood during acute hiv infection persists despite prompt initiation of art. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/1d2a126202fa4f6dbc8e432b92230853 |
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