{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T01:30:08Z","timestamp":1788485408698,"version":"build-2803163510"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T00:00:00Z","timestamp":1495756800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1"},{"start":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T00:00:00Z","timestamp":1495756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:p>Hepatitis B virus (HBV) infection shows significant gender\u2010related differences in pathogenesis, disease progression, and development of hepatocellular carcinoma. The gender\u2010associated differences in HBV replication and viral protein levels may be associated with distinct HBV\u2010specific immune responses in the host. In the present study, we examined the impact of gender on HBV\u2010specific immune responses in two different mouse models representing transient and persistent hepadnaviral infection; hydrodynamic injection with the HBV genome mimicked acute HBV infection, whereas the efficacy of therapeutic vaccination was studied in the woodchuck hepatitis virus transgenic mouse model. Consistent with previous reports, significantly higher HBV DNA and protein levels were detected in male compared to female mice. Although hydrodynamic injection with the HBV genome resulted in similar numbers of intrahepatic HBV\u2010specific cluster of differentiation 8\u2013positive (CD8<jats:sup>+<\/jats:sup>) T cells, their functionality was significantly reduced in males and correlated with higher numbers of intrahepatic regulatory T cells (Tregs). Similar effects were observed in woodchuck hepatitis virus transgenic mice immunized with a DNA prime\u2010recombinant adenovirus boost vaccination protocol. Male mice showed functionally suppressed woodchuck hepatitis virus\u2013specific CD8<jats:sup>+<\/jats:sup> T\u2010cell responses in the liver and significantly higher numbers of intrahepatic Tregs compared to females. Blockade of Treg responses in male mice led to augmented effector functions of specific CD8<jats:sup>+<\/jats:sup> T cells and subsequently improved virus control in both models of transient and persistent hepadnaviral infection. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: The functionality of virus\u2010specific CD8<jats:sup>+<\/jats:sup> T cells in male mice was suppressed by intrahepatic Tregs and inversely correlated with levels of hepadnaviral DNA and viral protein; the induction of intrahepatic Tregs by viral replication and\/or protein levels may explain the gender\u2010related differences in the outcomes of HBV infection and limit the success of immunotherapeutic strategies in male patients. (H<jats:sc>epatology<\/jats:sc> 2017;66:69\u201383).<\/jats:p>","DOI":"10.1002\/hep.29155","type":"journal-article","created":{"date-parts":[[2017,3,14]],"date-time":"2017-03-14T18:22:24Z","timestamp":1489515744000},"page":"69-83","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":49,"title":["Low hepatitis B virus\u2013specific T\u2010cell response in males correlates with high regulatory T\u2010cell numbers in murine models"],"prefix":"10.1097","volume":"66","author":[{"given":"Anna D.","family":"Kosinska","sequence":"first","affiliation":[{"name":"Institute of Virology, University Hospital of Essen,University Duisburg\u2010Essen,Essen,Germany"},{"name":"Key Laboratory of Medical Molecular Virology, Shanghai Public Health Clinical Center,Shanghai Medical College of Fudan University,Shanghai,People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Pishraft\u2010Sabet","sequence":"additional","affiliation":[{"name":"Institute of Virology, University Hospital of Essen,University Duisburg\u2010Essen,Essen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weimin","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Virology, University Hospital of Essen,University Duisburg\u2010Essen,Essen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Fang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology, Shanghai Public Health Clinical Center,Shanghai Medical College of Fudan University,Shanghai,People's Republic of China"},{"name":"Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences,Shanghai Medical College of Fudan University,Shanghai,People's Republic of 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Shanghai Public Health Clinical Center,Shanghai Medical College of Fudan University,Shanghai,People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thekla","family":"Kemper","sequence":"additional","affiliation":[{"name":"Institute of Virology, University Hospital of Essen,University Duisburg\u2010Essen,Essen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Virology, University Hospital of Essen,University Duisburg\u2010Essen,Essen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiou\u2010Hwei","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Microbiology,National Taiwan University College of Medicine,Taipei,Taiwan"},{"name":"NTU Center for Genomic Medicine,National Taiwan University College of 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