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Here, we investigated the viral protein expression, replication, and virion production using endoplasmic reticulum (ER) stress\u2010modulating chemicals, tunicamycin (an ER\u2010stress inducer), and salubrinal (an ER\u2010stress inhibitor). We found that ER\u2010stress could be induced by HBV replication in transfected HepG2 cells as well as by tunicamycin as demonstrated by dual luciferase assay. HBV intracellular core\u2010associated DNA quantified by qPCR has been significantly increased by tunicamycin in transfected HepG2 cells. Inversely, intracellular core associated and extracellular particle DNA has been significantly decreased in a dose\u2010dependent manner in salubrinal\u2010treated HepG2 cells transfected with HBV\u2010replicating plasmid pHBI. Similar results were found in stably HBV\u2010expressing hepatoblastoma (HB611) cells treated with salubrinal. However, increased or decreased ER\u2010stress by tunicamycin or salubrinal treatment, respectively, has been confirmed by expression analysis of grp78 using Western blot. In addition, Western blot results demonstrated that the expression of HBV core protein and large HBsAg is increased and decreased by tunicamycin and salubrinal, respectively. In conclusion, the sal\u2010mediated inhibition of the HBV replication and virion production might be due to the simultaneous reduction of core and large HBsAg expression and maintaining the ER homeostasis. These results of HBV replication regulation by modulation of ER\u2010stress dynamics would be useful for designing\/identifying anti\u2010HBV drugs targeting cellular signaling pathways.<\/jats:p>","DOI":"10.1155\/2024\/9117453","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T11:34:35Z","timestamp":1725017675000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Regulation of Hepatitis B Virus Replication by Modulating Endoplasmic Reticulum Stress (ER\u2010Stress)"],"prefix":"10.1155","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1487-5444","authenticated-orcid":false,"given":"Md. 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