Evidence map›Paper›PMID 40995214›Full record

ArticleFrontiers in aging2025

Reversal of perturbed DNA damage response and HIV latency by a histone methyltransferase inhibitor in virally suppressed individuals living with HIV.

Pragati Chavan, Sathi Koar, Rohini Bingewar, Anuja Sonawane, Jyoti Sawant, Pallavi Shidhaye, Amrita Rao, Rajani Bagul, Ujjwala Ghule, Sunita Kumbhar and 2 more

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Article in Frontiers in aging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Pragati ChavanICMR-National Institute of Translational Virology and AIDS Research (formerly ICMR-National AIDS Research Institute), Pune, India.
Sathi KoarICMR-National Institute of Translational Virology and AIDS Research (formerly ICMR-National AIDS Research Institute), Pune, India.
Rohini BingewarICMR-National Institute of Translational Virology and AIDS Research (formerly ICMR-National AIDS Research Institute), Pune, India.
Anuja SonawaneICMR-National Institute of Translational Virology and AIDS Research (formerly ICMR-National AIDS Research Institute), Pune, India.
Jyoti SawantICMR-National Institute of Translational Virology and AIDS Research (formerly ICMR-National AIDS Research Institute), Pune, India.
Pallavi ShidhayeICMR-National Institute of Translational Virology and AIDS Research (formerly ICMR-National AIDS Research Institute), Pune, India.
Amrita RaoICMR-National Institute of Translational Virology and AIDS Research (formerly ICMR-National AIDS Research Institute), Pune, India.
Rajani BagulICMR-National Institute of Translational Virology and AIDS Research (formerly ICMR-National AIDS Research Institute), Pune, India.
Ujjwala GhuleICMR-National Institute of Translational Virology and AIDS Research (formerly ICMR-National AIDS Research Institute), Pune, India.
Sunita KumbharICMR-National Institute of Translational Virology and AIDS Research (formerly ICMR-National AIDS Research Institute), Pune, India.
Manisha GhateICMR-National Institute of Translational Virology and AIDS Research (formerly ICMR-National AIDS Research Institute), Pune, India.
Ashwini SheteICMR-National Institute of Translational Virology and AIDS Research (formerly ICMR-National AIDS Research Institute), Pune, India.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Oxidative stress contributes to DNA damage, further leading to cellular senescence. HIV infection increases oxidative stress and interferes in DNA damage response. Hence, a study was conducted to assess the extent of DNA damage by evaluating global methylation, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and prelamin A levels in people living with HIV (PLHIV), representing alterations at the genetic, epigenetic, and structural levels. We also investigated the effect of methylation modulators on these markers and HIV latency reversal. Methods: Middle-aged virally suppressed PLHIV on long-term antiretroviral therapy (ART) and non-infected controls were enrolled for the study. The levels of 5-methylcytosine in blood and plasma 8-OHdG were assessed using commercially available colorimetric and ELISA kits, respectively. Reactive oxygen species (ROS) and prelamin A expression in T cells were assessed by flow cytometry. The levels of DNA damage markers were analyzed for their correlation with immunosenescent and inflammatory markers. Samples were treated with RG108 and chaetocin to assess their effect on these markers and HIV reactivation. HIV reactivation was assessed by the expression of intracellular P24 by flow cytometry and gag copies by real-time PCR. Results: PLHIV had significantly lower global DNA methylation levels and higher 8-OHdG and prelamin A levels than their age-matched HIV-uninfected controls. The ROS levels did not differ significantly among them. Global methylation and prelamin A levels correlated with immunosenescent T cells. The 8-OHdG levels correlated positively with angiotensin-II levels and negatively with proinflammatory cytokines. Treatment with chaetocin increased the global methylation levels and diminished prelamin A accumulation in CD4 Conclusion: PLHIV on ART had higher DNA damage-related markers despite having comparable ROS levels than their age-matched controls. The immunotherapeutic potential of chaetocin for reversing premature aging as well as HIV latency needs to be explored further.

Indexed as

8-OHdGglobal DNA hypomethylationoxidative stressPLHIVprelamin A

Identifiers

PMID40995214
PMCPMC12454357

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.