{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T18:59:00Z","timestamp":1774983540271,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T00:00:00Z","timestamp":1678752000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072357"],"award-info":[{"award-number":["82072357"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LQ20H200002"],"award-info":[{"award-number":["LQ20H200002"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Immunoregulation plays pivotal roles during chronic hepatitis B virus (HBV) infection. Studies have shown that Interleukin (IL)\u201035 is an important molecule associated with inadequate immune response against HBV. However, the mechanisms involved in the up\u2010regulation of IL\u201035 expression during persistent HBV infection remain unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we constructed a plasmid expressing the HBV X protein (pCMV\u2010HBx) to evaluate the relationship between HBx and IL\u201035. Activation of the JNK\/c\u2010Jun pathway was analyzed and chromatin immunoprecipitation followed by sequencing and luciferase reporter assays were performed to determine whether c\u2010Jun could regulate IL\u201035 transcription.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HBx can significantly activate <jats:italic>IL\u201035<\/jats:italic> promoter in both LO2 and HepG2 cells compared to the control plasmid (pCMV\u2010Tag2) using the dual\u2010luciferase assay. Whereas other viral proteins, such as S, preS1, the core protein, had no significant effect on IL\u201035 expression. Similarly, WB and qRT\u2010PCR also showed that HBx can significantly promote IL\u201035 expression at protein and mRNA levels in the aforementioned cells. The relevant pathway mechanism showed that the expression of JNK and c\u2010Jun genes was significantly higher in transfected cells carrying pCMV\u2010HBx than in the pCMV\u2010Tag2\u2010transfected and \u2010untransfected cells. WB analysis revealed that phosphorylated JNK and c\u2010Jun were overexpressed after HBx action. Conversely, the addition of the JNK\/c\u2010Jun signaling pathway inhibitor could significantly suppress HBx\u2010induced IL\u201035 expression in a dose\u2010dependent manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A novel molecular mechanism of HBV\u2010induced IL\u201035 expression was revealed, which involves JNK\/c\u2010Jun signaling in up\u2010regulating IL\u201035 expression via HBx, resulting in transactivation of the IL\u201035 subunit <jats:italic>EBI3<\/jats:italic> and <jats:italic>p35<\/jats:italic> promoter.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24860","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T12:31:17Z","timestamp":1678797077000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["JNK\/c\u2010Jun pathway activation is essential for HBx\u2010induced IL\u201035 elevation to promote persistent HBV infection"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2989-3477","authenticated-orcid":false,"given":"Xuefen","family":"Li","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, the First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaoyun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Central Laboratory, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, the First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, the First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunxia","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuejiao","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, the First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated 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