{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:24:01Z","timestamp":1792679041666,"version":"4.5.0"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2007,4,15]],"date-time":"2007-04-15T00:00:00Z","timestamp":1176595200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2007,4,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Dysfunctional CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells present in chronic virus infections can express programmed death 1 (PD-1) molecules, and the inhibition of the engagement of PD-1 with its ligand (PD-L1) has been reported to enhance the antiviral function of these T cells. We took advantage of the wide fluctuations in levels of viremia which are typical of chronic hepatitis B virus (HBV) infection to comprehensively analyze the impact of prolonged exposure to different virus quantities on virus-specific T-cell dysfunction and on its reversibility through the blocking of the PD-1\/PD-L1 pathway. We confirm that chronic HBV infection has a profound effect on the HBV-specific T-cell repertoire. Despite the use of a comprehensive panel of peptides covering all HBV proteins, HBV-specific T cells were rarely observed directly ex vivo in samples from patients with chronic infection, in contrast to those from patients with acute HBV infection. In chronic HBV infection, virus-specific T cells were detected mainly in patients with lower levels of viremia. These HBV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells expressed PD-1, and their function was improved by the blocking of PD-1\/PD-L1 engagement. Thus, a broad spectrum of anti-HBV immunity is expressed by patients with chronic HBV infection and this spectrum is proportional to HBV replication levels and can be improved by blocking the PD-1\/PD-L1 pathway. This information may be useful for the design of immunotherapeutic strategies to complement and optimize available antiviral therapies.\n                  <\/jats:p>","DOI":"10.1128\/jvi.02844-06","type":"journal-article","created":{"date-parts":[[2007,2,7]],"date-time":"2007-02-07T20:19:35Z","timestamp":1170879575000},"page":"4215-4225","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":842,"title":["Characterization of Hepatitis B Virus (HBV)-Specific T-Cell Dysfunction in Chronic HBV Infection"],"prefix":"10.1128","volume":"81","author":[{"given":"Carolina","family":"Boni","sequence":"first","affiliation":[{"name":"Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Fisicaro","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Valdatta","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Amadei","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Di Vincenzo","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Giuberti","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diletta","family":"Laccabue","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Zerbini","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albertina","family":"Cavalli","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Missale","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Bertoletti","sequence":"additional","affiliation":[{"name":"Centre of Molecular Medicine, Agency for Science, Technology and Research, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04444"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01354-06"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.23.10445"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.3.933"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.7.3532-3540.2006"},{"key":"e_1_3_2_7_2","first-page":"263","volume":"36","year":"2002","unstructured":"Brunetto, M. 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