Led by Director SHIN Eui-Cheol, the team at the Institute for Basic Science (IBS) Korea Virus Research Institute’s (KVRI) Center for Viral Immunology has brought to light significant insights regarding the persistent effects of chronic Hepatitis C virus (HCV) infection on the immune system, which endure even after successful treatment. The research revealed that “epigenetic scars” linger in the regulatory T cells, which show inflammatory traits long after the virus is eliminated. This occurs despite the use of highly effective direct-acting antivirals (DAAs), which have markedly increased cure rates for this disease.
The focus of the study was on patients who achieved a sustained virologic response (SVR) from DAA treatment. SVR, determined when no HCV is detectable in the blood 12 weeks post-treatment, strongly indicates the virus’s eradication. However, the study observed that the frequency of activated regulatory T cells (TREG) remained elevated during and after treatment, suggesting that the immune system does not fully recover even without the virus.
In-depth analyses, including RNA sequencing and ATAC-seq, showed that the transcriptomic and epigenetic landscapes of TREG cells from HCV patients remained altered long after the virus was eradicated. These cells exhibited prolonged inflammatory responses, such as increased TNF signalling, indicating long-term changes induced by the chronic infection. These activated TREG cells from HCV patients continued to produce inflammatory cytokines like TNF, IFN-γ, and IL-17A even after the virus was cleared.
The persistence of these inflammatory features in TREG cells has significant implications for the long-term management of patients treated for chronic HCV infection. Despite successful viral clearance, the continued immune system dysregulation suggests a potential for ongoing chronic inflammation and related health issues. Director SHIN Eui Cheol emphasized the importance of monitoring even after eradicating the virus to understand and fully manage these persistent immune changes.
The research team is now focusing on further investigating the mechanisms behind the sustained inflammatory state of TREG cells. By exploring potential therapeutic interventions that could reverse these epigenetic and transcriptomic changes, they aim to develop more effective strategies to ensure complete recovery and improve the quality of life for HCV patients.
Additionally, Director Shin highlighted an interest in whether other chronic viral infections might cause long-lasting epigenetic changes in the immune system. Identifying the clinical implications of these persistent immune alterations remains one of the team’s primary goals, potentially leading to broader applications in managing chronic viral infections beyond HCV.
More information: So-Young Kim et al, Epigenetic scars in regulatory T cells are retained after successful treatment of chronic hepatitis C with direct-acting antivirals, Journal of Hepatology. DOI: 10.1016/j.jhep.2024.06.011
Journal information: Journal of Hepatology Provided by Institute for Basic Science
