<mods:mods xmlns:mods="http://www.loc.gov/mods/v3" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-7.xsd"><mods:titleInfo><mods:title>Characterizing the Impact of 5’ PreS1 Deletion Hepatitis B Virus Mutants on Endoplasmic Reticulum Stress</mods:title></mods:titleInfo><mods:typeOfResource authority="primo">dissertations</mods:typeOfResource><mods:name type="personal"><mods:namePart>Luong, Selena</mods:namePart><mods:role><mods:roleTerm type="text">creator</mods:roleTerm></mods:role></mods:name><mods:name type="personal"><mods:namePart>Li, Jisu</mods:namePart><mods:role><mods:roleTerm type="text">Advisor</mods:roleTerm></mods:role></mods:name><mods:name type="personal"><mods:namePart>Tong, Shuping</mods:namePart><mods:role><mods:roleTerm type="text">Reader</mods:roleTerm></mods:role></mods:name><mods:name type="personal"><mods:namePart>Dugan, Aisling</mods:namePart><mods:role><mods:roleTerm type="text">Reader</mods:roleTerm></mods:role></mods:name><mods:name type="corporate"><mods:namePart>Brown University. Biology and Medicine: Biotechnology</mods:namePart><mods:role><mods:roleTerm type="text">sponsor</mods:roleTerm></mods:role></mods:name><mods:originInfo><mods:copyrightDate>2025</mods:copyrightDate></mods:originInfo><mods:physicalDescription><mods:extent>, None p.</mods:extent><mods:digitalOrigin>born digital</mods:digitalOrigin></mods:physicalDescription><mods:note type="thesis">Thesis (Sc. M.)--Brown University, 2025</mods:note><mods:genre authority="aat">theses</mods:genre><mods:abstract>Hepatitis 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.</mods:abstract><mods:subject authority="fast" authorityURI="http://id.worldcat.org/fast" valueURI="http://id.worldcat.org/fast/01167670"><mods:topic>Virology</mods:topic></mods:subject><mods:subject><mods:topic>HBV infection</mods:topic></mods:subject><mods:subject><mods:topic>ER stress</mods:topic></mods:subject><mods:language><mods:languageTerm authority="iso639-2b">English</mods:languageTerm></mods:language><mods:recordInfo><mods:recordContentSource authority="marcorg">RPB</mods:recordContentSource><mods:recordCreationDate encoding="iso8601">20250707</mods:recordCreationDate></mods:recordInfo></mods:mods>