Altered NK Cell Phenotype in Tenofovir-Treated Chronic Hepatitis B Patients and Identification of Genes Regulating the mTOR Pathway 9203

Abstract Description Chronic Hepatitis B (CHB) remains a significant global health burden, with its prevalence continuing to rise according to the World Health Organization (WHO). Persistent infection and disease chronicity are strongly linked to immune system dysregulation, particularly in Natural Killer (NK) cells. These immune cells play a critical role in controlling hepatitis B virus (HBV) through the production of IFN-gamma and the elimination of infected cells. However, in untreated CHB, HBV impairs NK cell function, including suppression of the mTOR signaling pathway—a pivotal regulator of cellular metabolism and immune responses—facilitating viral persistence and chronic infection. This study investigates phenotypic alterations in NK cells within cohorts of tenofovir-treated and untreated CHB patients. We observed notable therapy-associated changes in NK cell activation, cytotoxicity, and metabolic markers. Concurrently, we observed that HBV targets specific mTOR-regulatory genes to compromise NK cell functionality. These insights provide a deeper understanding of the immune dysregulation in CHB and identify potential molecular targets for therapeutic intervention. Future studies will elucidate the precise mechanisms by which HBV modulates mTOR-related pathways to inform the development of strategies aimed at restoring NK cell function and improving clinical outcomes. Funding Sources NCI U54CA132378 Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)