Characterizing the Impact of 5’ PreS1 Deletion Hepatitis B Virus Mutants on Endoplasmic Reticulum StressdissertationsLuong, SelenacreatorLi, JisuAdvisorTong, ShupingReaderDugan, AislingReaderBrown University. Biology and Medicine: Biotechnologysponsor2025, None p.born digitalThesis (Sc. M.)--Brown University, 2025thesesHepatitis B Virus (HBV) remains a significant global health burden, chronically infecting over 350 million individuals worldwide and increasing the risk of severe liver complications, including hepatocellular carcinoma (HCC) and liver cirrhosis. Additionally, chronic infection of HBV can lead to an accumulation of mutations within the viral genome, some of which have been implicated in disease progression. Notably, in-frame deletions in the preS1 region of the envelope gene have been associated with increased viral infectivity and pathogenicity. In this study, we investigated the effects of a 5’ preS1 deletion mutant of genotype C origin on ER stress in hepatocytes, which is a common feature prior to cancer development. We specifically examined the expression levels of key ER stress responsible genes, including GRP78, GADD153, and ATF6, to determine whether the mutant induces a more pronounced ER stress response compared to the wild-type virus in hepatoma cell lines Huh7 and HepG2 after co-transfection of the reporter gene with HBV DNA. Additionally, HBsAg production was assessed as an indicator of viral replication and protein expression of the mutant, providing insight into how preS1 mutations may contribute to HBV persistence and pathogenicity. Lastly, the clinical relevance of the 5’ preS1 mutant was assessed by measuring the ER stress levels in chronically infected liver cells in vitro. By elucidating the mechanisms by which preS1 deletions contribute to liver injury, this study provides new insights into the molecular underpinnings of HBV-induced liver disease. A deeper understanding of these processes is crucial for developing targeted therapeutic interventions, ultimately reducing the public health burden associated with chronic HBV infection.VirologyHBV infectionER stressEnglishRPB20250707