{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T04:24:59Z","timestamp":1782707099260,"version":"3.54.5"},"reference-count":55,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,15]],"date-time":"2024-06-15T00:00:00Z","timestamp":1718409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Pusan National University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hepatitis B virus (HBV) infects approximately 300 million people worldwide, causing chronic infections. The HBV X protein (HBx) is crucial for viral replication and induces reactive oxygen species (ROS), leading to cellular damage. This study explores the relationship between HBx-induced ROS, p53 activation, and HBV replication. Using HepG2 and Hep3B cell lines that express the HBV receptor NTCP, we compared ROS generation and HBV replication relative to p53 status. Results indicated that HBV infection significantly increased ROS levels in p53-positive HepG2-NTCP cells compared to p53-deficient Hep3B-NTCP cells. Knockdown of p53 reduced ROS levels and enhanced HBV replication in HepG2-NTCP cells, whereas p53 overexpression increased ROS and inhibited HBV replication in Hep3B-NTCP cells. The ROS scavenger N-acetyl-L-cysteine (NAC) reversed these effects. The study also found that ROS-induced degradation of the HBx is mediated by the E3 ligase Siah-1, which is activated by p53. Mutations in p53 or inhibition of its transcriptional activity prevented ROS-mediated HBx degradation and HBV inhibition. These findings reveal a p53-dependent negative feedback loop where HBx-induced ROS increases p53 levels, leading to Siah-1-mediated HBx degradation and HBV replication inhibition. This study offers insights into the molecular mechanisms of HBV replication and identifies potential therapeutic targets involving ROS and p53 pathways.<\/jats:p>","DOI":"10.3390\/ijms25126606","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T11:14:16Z","timestamp":1718622856000},"page":"6606","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Reactive Oxygen Species Induction by Hepatitis B Virus: Implications for Viral Replication in p53-Positive Human Hepatoma Cells"],"prefix":"10.3390","volume":"25","author":[{"given":"Yuna","family":"Jeong","sequence":"first","affiliation":[{"name":"Department of Integrated Biological Science, The Graduate School, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwoo","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Integrated Biological Science, The Graduate School, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0905-3267","authenticated-orcid":false,"given":"Kyung Lib","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Integrated Biological Science, The Graduate School, Pusan National University, Busan 46241, Republic of Korea"},{"name":"Department of Microbiology, College of Natural Science, Pusan National University, Busan 46241, Republic of Korea"},{"name":"Microbiological Resource Research Institute, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1016\/j.vaccine.2011.12.116","article-title":"Global epidemiology of hepatitis B virus infection: New estimates of age-specific HBsAg seroprevalence and endemicity","volume":"30","author":"Ott","year":"2012","journal-title":"Vaccine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3851\/IMP1619","article-title":"Molecular genetics of HBV infection","volume":"15","author":"Locarnini","year":"2010","journal-title":"Antivir. 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