{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T06:37:14Z","timestamp":1764139034181,"version":"3.46.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hepatitis B virus (HBV) infection continues to pose a significant global health challenge, affecting millions of individuals worldwide. Persistent HBV infection is acknowledged as a complex and polygenic process influenced by virological, environmental, and host genetic factors. Previous in vitro studies have indicated that INTS10 inhibits HBV replication in a manner dependent on interferon regulatory factor 3 (IRF3). Nevertheless, the relationships among INTS10 expression, IRF3, and HBV replication in patients with chronic hepatitis B (CHB) have not been comprehensively examined. Thus, this study aimed to investigate the associations between INTS10, IRF3, and HBV replication in CHB patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 127 treatment-na\u00efve CHB patients were recruited and categorized into hepatitis B e antigen (HBeAg)-negative and HBeAg-positive groups. Quantitative PCR was utilized to quantify INTS10 and IRF3 expression levels, alongside serum HBV DNA load and conventional liver biochemical parameters, to evaluate HBV infection status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings revealed significantly lower expression levels of both INTS10 and IRF3 in HBeAg-positive patients compared to their HBeAg-negative counterparts. Additionally, a positive correlation was observed between IRF3 and INTS10 expression. In HBeAg-positive CHB patients, INTS10 and IRF3 levels exhibited negative correlations with HBV DNA, HBeAg, hepatitis B surface antigen (HBsAg), and total bile acid (TBA) levels. Conversely, no significant correlations were detected between INTS10 or IRF3 and these virological and biochemical markers in HBeAg-negative patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These results suggest that the relationship between INTS10 and IRF3 expression may be modulated by HBeAg status. This implies a potential involvement of HBeAg in the antiviral mechanisms mediated by INTS10 and IRF3 in CHB. Consequently, our study offers valuable insights that may contribute to enhanced clinical management of HBV infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2025.1609297","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T06:34:35Z","timestamp":1764138875000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Expression and significance of INTS10 and IRF3 in chronic hepatitis B patients"],"prefix":"10.3389","volume":"16","author":[{"given":"Aizhu","family":"Ye","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongbiao","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wennan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref23","doi-asserted-by":"publisher","first-page":"e0170419","DOI":"10.1371\/journal.pone.0170419","article-title":"N-glycosylation of the Na+-taurocholate Cotransporting polypeptide (NTCP) determines its trafficking and stability and is required for hepatitis B virus infection","volume":"12","author":"Appelman","year":"2017","journal-title":"PLoS One"},{"key":"ref1","doi-asserted-by":"publisher","first-page":"9072","DOI":"10.1126\/sciadv.aaz9072","article-title":"Integrator restrains paraspeckles assembly by promoting isoform switching of the lncRNA NEAT1","volume":"6","author":"Barra","year":"2020","journal-title":"Sci. Adv."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1186\/s12964-025-02256-2","article-title":"The cancer-associated fibroblast facilitates YAP liquid-liquid phase separation to promote cancer cell stemness in HCC","volume":"23","author":"Chen","year":"2025","journal-title":"Cell Commun. Signaling"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1016\/j.jhep.2025.03.018","article-title":"EASL clinical practice guidelines on the management of hepatitis B virus infection","volume":"83","author":"Cornberg","year":"2025","journal-title":"J. Hepatol."},{"key":"ref4","first-page":"5395","article-title":"Clinical implication of long non-coding RNA NEAT1 expression in hepatocellular carcinoma patients. Int","volume":"8","author":"Guo","year":"2015","journal-title":"J Clin Exp Pathol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"67241","DOI":"10.18632\/oncotarget.18589","article-title":"Genetic profile and biological implication of PIN2\/TRF1-interacting telomerase inhibitor 1 (PinX1) in human cancers: an analysis using the Cancer genome atlas","volume":"8","author":"Huang","year":"2017","journal-title":"Oncotarget"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"592","DOI":"10.3390\/v12060592","article-title":"Hepatitis B virus DNA is a substrate for the cGAS\/STING pathway but is not sensed in infected hepatocytes","volume":"12","author":"Lauterbach-Rivi\u00e8re","year":"2020","journal-title":"Viruses"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"101969","DOI":"10.1016\/j.isci.2020.101969","article-title":"Suppression of hepatitis B virus through therapeutic activation of RIG-I and IRF3 signaling in hepatocytes","volume":"24","author":"Lee","year":"2021","journal-title":"iScience"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/bs.apha.2015.04.003","article-title":"Bile acid metabolism and signaling in cholestasis","volume":"74","author":"Li","year":"2015","journal-title":"Inflammation Cancer."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1186\/s12885-024-12926-y","article-title":"Single-cell sequencing analysis revealed that NEAT1 was a potential biomarker and therapeutic target of prostate cancer","volume":"24","author":"Li","year":"2024","journal-title":"BMC Cancer"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/ncomms11664","article-title":"Genome-wide association study identifies 8p21.3 associated with persistent hepatitis B virus infection among Chinese","volume":"7","author":"Li","year":"2016","journal-title":"Nat. Commun."},{"key":"ref11","doi-asserted-by":"crossref","DOI":"10.1039\/D5MD00468C","volume-title":"The lignan compound matairesinol monoglucoside induces type I interferon production in HBV infection immunity by regulating STING signaling","author":"Lin","year":"2025"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"11853","DOI":"10.1074\/jbc.RA118.007179","article-title":"Increased sulfation of bile acids in mice and human subjects with sodium taurocholate cotransporting polypeptide deficiency","volume":"294","author":"Mao","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/j.tibs.2020.07.004","article-title":"The integrator complex in transcription and development","volume":"45","author":"Mendoza-Figueroa","year":"2020","journal-title":"Trends Biochem. Sci."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"a028423","DOI":"10.1101\/cshperspect.a028423","article-title":"The interferon (IFN) class of cytokines and the IFN regulatory factor (IRF) transcription factor family","volume":"10","author":"Negishi","year":"2018","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1002\/hep.27159","article-title":"Binding of hepatitis B virus to its cellular receptor alters the expression profile of genes of bile acid metabolism","volume":"60","author":"Oehler","year":"2014","journal-title":"Hepatology"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"8161","DOI":"10.3748\/wjg.v22.i36.8161","article-title":"Impact of hepatitis B virus infection on hepatic metabolic signaling pathway","volume":"22","author":"Shi","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"12193","DOI":"10.1073\/pnas.1412631111","article-title":"Modeling host interactions with hepatitis B virus using primary and induced pluripotent stem cell-derived hepatocellular systems","volume":"111","author":"Shlomai","year":"2014","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.mehy.2007.08.032","article-title":"The \u201cmetabolovirus\u201d model of hepatitis B virus suggests nutritional therapy as an effective anti-viral weapon","volume":"71","author":"Shlomai","year":"2008","journal-title":"Med. Hypotheses"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"7703","DOI":"10.1080\/21645515.2025.2567703","article-title":"PV-10 enhances immune responses in hepatitis B vaccination through STING pathway","volume":"21","author":"Sipila","year":"2025","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1631","DOI":"10.1002\/hep.29251","article-title":"Hepatic uptake of conjugated bile acids is mediated by both sodium taurocholate cotransporting polypeptide and organic anion transporting polypeptides and modulated by intestinal sensing of plasma bile acid levels in mice","volume":"66","author":"Slijepcevic","year":"2017","journal-title":"Hepatology"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1341651","DOI":"10.3389\/fphar.2024.1341651","article-title":"Chishao (Paeoniae Radix Rubra) alleviates intra-hepatic cholestasis by modulating NTCP in rats","volume":"15","author":"Sun","year":"2024","journal-title":"Front. Pharmacol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/cmi.2010.36","article-title":"Hepatitis B virus X protein suppresses virus-triggered IRF3 activation and IFN-\u03b2 induction by disrupting the VISA-associated complex","volume":"7","author":"Wang","year":"2010","journal-title":"Cell. Mol. Immunol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1002\/mc.23328","article-title":"Effects of genetic polymorphisms in INTS10 and their interaction with environmental factors on progression from persistent HBV infection to hepatocellular carcinoma","volume":"60","author":"Wu","year":"2021","journal-title":"Mol. Carcinog."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.cca.2019.12.020","article-title":"Albumin-bilirubin score is associated with response to pegylated interferon and nucleos(t)ide analogues in chronic hepatitis B patients","volume":"502","author":"Xun","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"52718","DOI":"10.1038\/s41467-024-52718-3","article-title":"Liver mechanosignaling as a natural anti-hepatitis B virus mechanism","volume":"15","author":"Ye","year":"2024","journal-title":"Nat. Commun."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e22886","DOI":"10.1002\/jcla.22886","article-title":"Toll-like receptors, long non-coding RNA NEAT1, and RIG-I expression are associated with HBeAg-positive chronic hepatitis B patients in the active phase","volume":"33","author":"Zeng","year":"2019","journal-title":"J. Clin. Lab. Anal."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1609297\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T06:34:36Z","timestamp":1764138876000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1609297\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,26]]},"references-count":27,"alternative-id":["10.3389\/fmicb.2025.1609297"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2025.1609297","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,26]]},"article-number":"1609297"}}