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  • Epigenetic Scars in TREG Cells Post-HCV Treatment

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    The number of regulatory T cells remains elevated in the peripheral blood of chronic hepatitis C patients, and this increase remains persistent even after the completion of treatment. Analysis of the transcriptome and epigenome of patients with chronic hepatitis C show that regulatory T cells continue to have increased inflammatory characteristics compared to normal people. These inflammatory TREG cells showed higher expression levels of activation markers and transcription factors such as RORγt and T-bet, leading them to secrete inflammatory cytokine TNF. (Image Credit: Institute for Basic Science)


    Researchers at the Institute for Basic Science (IBS) Korea Virus Research Institute’s (KVRI) Center for Viral Immunology, led by Director Shin Eui-Cheol, have uncovered critical findings regarding the enduring impact of chronic Hepatitis C virus (HCV) infection on the immune system, even after successful treatment. The study revealed the presence of “epigenetic scars” in regulatory T cells (TREG cells) that continue to exhibit inflammatory properties long after the virus has been eradicated.

    Chronic hepatitis C, a condition resulting from HCV infection, is known to cause severe liver complications, including cirrhosis and cancer. The introduction of direct-acting antivirals (DAAs) has markedly increased cure rates for this chronic infection. However, there is evidence suggesting that the immune system does not fully recover post-cure.

    Long-Term Effects of HCV on TREG Cells
    The study focused on patients with chronic HCV infection who achieved sustained virologic response (SVR) following DAA treatment. SVR is characterized by the absence of detectable HCV in the blood for 12 weeks after treatment, signifying effective eradication of the virus. Despite this, the researchers observed that the frequency of activated TREG cells remained elevated during and even after the virus was eliminated.

    Advanced analyses, including RNA sequencing and ATAC-seq, were conducted to explore the transcriptomic and epigenetic landscapes of TREG cells from these patients. Results showed that these cells retained altered profiles post-virus eradication, sustaining inflammatory features such as increased TNF signaling. These activated TREG cells continued to produce inflammatory cytokines like TNF, IFN-γ, and IL-17A even after HCV clearance, with these traits persisting for up to six years post-SVR.

    Implications for Long-Term Patient Management
    The findings suggest significant implications for the long-term management of chronic HCV patients, even after successful viral clearance. The persistent inflammatory properties in TREG cells could mean ongoing immune dysregulation, potentially leading to chronic inflammation and associated health issues. Eui-Cheol highlighted the research by stating, “Our findings highlight the need for ongoing monitoring even after HCV has been cleared. By understanding the underlying mechanisms of these persistent immune changes, we can develop more effective strategies to ensure complete recovery and improve the quality of life for HCV patients.”

    Future Research Directions
    The research team is now further investigating the mechanisms behind the sustained inflammatory state of TREG cells. They aim to identify potential therapeutic interventions to reverse these epigenetic and transcriptomic changes. Eui-Cheol remarked, “We are now interested in seeing whether other chronic viral infections also cause long-lasting epigenetic changes in our immune systems. One of our goals is to identify clinical implications of these persistent immune alterations.”



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