{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T22:19:39Z","timestamp":1757456379792,"version":"3.41.2"},"reference-count":57,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatitis B e antigen (HBeAg) seropositivity during the natural history of chronic hepatitis B (CHB) is known to coincide with significant increases in serum and intrahepatic HBV DNA levels. However, the precise underlying mechanism remains unclear. In this study, we found that PreC (HBeAg precursor) genetic ablation leads to reduced viral replication both in vitro and in vivo. Furthermore, PreC impedes the proteasomal degradation of HBV polymerase, promoting viral replication. We discovered that PreC interacts with SUV39H1, a histone methyltransferase, resulting in a reduction in the expression of Cdt2, an adaptor protein of CRL4 E3 ligase targeting HBV polymerase. SUV39H1 induces H3K9 trimethylation of the Cdt2 promoter in a PreC\u2010induced manner. CRISPR\u2010mediated knockout of endogenous SUV39H1 or pharmaceutical inhibition of SUV39H1 decreases HBV loads in the mouse liver. Additionally, genetic depletion of Cdt2 in the mouse liver abrogates PreC\u2010related HBV replication. Interestingly, a negative correlation of intrahepatic Cdt2 with serum HBeAg and HBV DNA load was observed in CHB patient samples. Our study thus sheds light on the mechanistic role of PreC in inducing HBV replication and identifies potential therapeutic targets for HBV treatment.<\/jats:p>","DOI":"10.1002\/jmv.29607","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T06:45:19Z","timestamp":1713336319000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["HBV PreC interacts with SUV39H1 to induce viral replication by blocking the proteasomal degradation of viral polymerase"],"prefix":"10.1002","volume":"96","author":[{"given":"Lidan","family":"Hou","sequence":"first","affiliation":[{"name":"Department of General Surgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China"},{"name":"Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases Hangzhou China"},{"name":"National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China"},{"name":"Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases Hangzhou China"},{"name":"National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liuxin","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China"},{"name":"Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases Hangzhou China"},{"name":"National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boqiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China"},{"name":"Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases Hangzhou China"},{"name":"National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shijie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China"},{"name":"Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases Hangzhou China"},{"name":"National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China"},{"name":"Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases Hangzhou China"},{"name":"National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songyi","family":"Li","sequence":"additional","affiliation":[{"name":"Animal Center, Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China"},{"name":"Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases Hangzhou China"},{"name":"National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China"},{"name":"Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China"},{"name":"Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China"},{"name":"Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases Hangzhou China"},{"name":"National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6457-0577","authenticated-orcid":false,"given":"Xiujun","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China"},{"name":"Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases Hangzhou China"},{"name":"National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"WHO:Hepatitis B.https:\/\/wwwwhoint\/news-room\/fact-sheets\/detail\/hepatitis-b 2022."},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.08.052"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00838-3"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-virology-110615-042238"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2020.104925"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.11.003"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23571"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31506"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01695-20"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.64.12.6141-6147.1990"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.1.37-45.1992"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.01653"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50012"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01123-14"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1631\/jzus.2005.B0236"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840380410"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.23.11354-11364.2001"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02575-13"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30844"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2002.05819.x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aau7130"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12250-015-3582-7"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa317"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.08.019"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1518090112"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.1997.tb00499.x"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.26025"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.7.3756-3762.1993"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.63.12.5238-5243.1989"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00667-18"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00196-19"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50453"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.11.050"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00111-14"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.1.345-353.1997"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1997.8594"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000335"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.83468-0"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.16.8524-8535.2004"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v11.i5.649"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2016.04.022"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr451"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.9.4077"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.5.3067-3073.1995"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2004.11.029"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.24064"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.29129"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.000590"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-022-10351-6"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2015.08.020"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31313"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2019455118"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26379"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00483-w"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2211855120"},{"key":"e_1_2_10_57_1","first-page":"170","article-title":"Distribution patterns of HP1, a heterochromatin\u2010associated nonhistone chromosomal protein of drosophila","volume":"50","author":"James TC","year":"1989","journal-title":"EJCB"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.06.023"}],"container-title":["Journal of Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.29607","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T19:15:52Z","timestamp":1744917352000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmv.29607"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4]]},"references-count":57,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1002\/jmv.29607"],"URL":"https:\/\/doi.org\/10.1002\/jmv.29607","archive":["Portico"],"relation":{},"ISSN":["0146-6615","1096-9071"],"issn-type":[{"type":"print","value":"0146-6615"},{"type":"electronic","value":"1096-9071"}],"subject":[],"published":{"date-parts":[[2024,4]]},"assertion":[{"value":"2024-01-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e29607"}}