Immunobiology of hepatitis B virus infection
The adaptive immune response, particularly the virus‐specific CD8+ T‐cell response, is largely responsible for viral clearance and disease pathogenesis during hepatitis B virus (HBV) infection. The HBV‐specific CD8+ T‐cell response is vigorous, polyclonal and multispecific in acutely infected patien...
Saved in:
| Published in | Hepatology research Vol. 45; no. 2; pp. 179 - 189 |
|---|---|
| Main Authors | , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Blackwell Publishing Ltd
01.02.2015
|
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | The adaptive immune response, particularly the virus‐specific CD8+ T‐cell response, is largely responsible for viral clearance and disease pathogenesis during hepatitis B virus (HBV) infection. The HBV‐specific CD8+ T‐cell response is vigorous, polyclonal and multispecific in acutely infected patients who successfully clear the virus and relatively weak and narrowly focused in chronically infected patients. The immunological basis for this dichotomy is unclear. A recent study using HBV transgenic mice and HBV‐specific T‐cell receptor transgenic mice suggests that intrahepatic antigen presentation by HBV positive hepatocytes suppresses HBV‐specific CD8+ T‐cell responses through a co‐inhibitory molecule, programmed cell death 1 (PD‐1). In contrast, antigen presentation by activated professional antigen‐presenting cells induces functional differentiation of HBV‐specific CD8+ T cells. These findings suggest that the outcome of T‐cell priming is largely dependent on the nature of antigen‐presenting cells. Another study suggests that the timing of HBV‐specific CD4+ T‐cell priming regulates the magnitude of the HBV‐specific CD8+ T‐cell response. Other factors that could regulate HBV‐specific cellular immune responses are high viral loads, mutational epitope inactivation, T‐cell receptor antagonism and infection of immunologically privileged tissues. However, these pathways become apparent only in the setting of an ineffective cellular immune response, which is therefore the fundamental underlying cause. Understanding the cellular and molecular mechanisms by which HBV evades host immune responses will eventually help develop new immunotherapeutic strategies designed to terminate chronic HBV infection. |
|---|---|
| AbstractList | The adaptive immune response, particularly the virus-specific CD8(+) T-cell response, is largely responsible for viral clearance and disease pathogenesis during hepatitis B virus (HBV) infection. The HBV-specific CD8(+) T-cell response is vigorous, polyclonal and multispecific in acutely infected patients who successfully clear the virus and relatively weak and narrowly focused in chronically infected patients. The immunological basis for this dichotomy is unclear. A recent study using HBV transgenic mice and HBV-specific T-cell receptor transgenic mice suggests that intrahepatic antigen presentation by HBV positive hepatocytes suppresses HBV-specific CD8(+) T-cell responses through a co-inhibitory molecule, programmed cell death 1 (PD-1). In contrast, antigen presentation by activated professional antigen-presenting cells induces functional differentiation of HBV-specific CD8(+) T cells. These findings suggest that the outcome of T-cell priming is largely dependent on the nature of antigen-presenting cells. Another study suggests that the timing of HBV-specific CD4(+) T-cell priming regulates the magnitude of the HBV-specific CD8(+) T-cell response. Other factors that could regulate HBV-specific cellular immune responses are high viral loads, mutational epitope inactivation, T-cell receptor antagonism and infection of immunologically privileged tissues. However, these pathways become apparent only in the setting of an ineffective cellular immune response, which is therefore the fundamental underlying cause. Understanding the cellular and molecular mechanisms by which HBV evades host immune responses will eventually help develop new immunotherapeutic strategies designed to terminate chronic HBV infection.The adaptive immune response, particularly the virus-specific CD8(+) T-cell response, is largely responsible for viral clearance and disease pathogenesis during hepatitis B virus (HBV) infection. The HBV-specific CD8(+) T-cell response is vigorous, polyclonal and multispecific in acutely infected patients who successfully clear the virus and relatively weak and narrowly focused in chronically infected patients. The immunological basis for this dichotomy is unclear. A recent study using HBV transgenic mice and HBV-specific T-cell receptor transgenic mice suggests that intrahepatic antigen presentation by HBV positive hepatocytes suppresses HBV-specific CD8(+) T-cell responses through a co-inhibitory molecule, programmed cell death 1 (PD-1). In contrast, antigen presentation by activated professional antigen-presenting cells induces functional differentiation of HBV-specific CD8(+) T cells. These findings suggest that the outcome of T-cell priming is largely dependent on the nature of antigen-presenting cells. Another study suggests that the timing of HBV-specific CD4(+) T-cell priming regulates the magnitude of the HBV-specific CD8(+) T-cell response. Other factors that could regulate HBV-specific cellular immune responses are high viral loads, mutational epitope inactivation, T-cell receptor antagonism and infection of immunologically privileged tissues. However, these pathways become apparent only in the setting of an ineffective cellular immune response, which is therefore the fundamental underlying cause. Understanding the cellular and molecular mechanisms by which HBV evades host immune responses will eventually help develop new immunotherapeutic strategies designed to terminate chronic HBV infection. The adaptive immune response, particularly the virus‐specific CD8 + T ‐cell response, is largely responsible for viral clearance and disease pathogenesis during hepatitis B virus ( HBV ) infection. The HBV ‐specific CD8 + T ‐cell response is vigorous, polyclonal and multispecific in acutely infected patients who successfully clear the virus and relatively weak and narrowly focused in chronically infected patients. The immunological basis for this dichotomy is unclear. A recent study using HBV transgenic mice and HBV ‐specific T ‐cell receptor transgenic mice suggests that intrahepatic antigen presentation by HBV positive hepatocytes suppresses HBV ‐specific CD8 + T ‐cell responses through a co‐inhibitory molecule, programmed cell death 1 ( PD ‐1). In contrast, antigen presentation by activated professional antigen‐presenting cells induces functional differentiation of HBV ‐specific CD8 + T cells. These findings suggest that the outcome of T ‐cell priming is largely dependent on the nature of antigen‐presenting cells. Another study suggests that the timing of HBV ‐specific CD4 + T ‐cell priming regulates the magnitude of the HBV ‐specific CD8 + T ‐cell response. Other factors that could regulate HBV ‐specific cellular immune responses are high viral loads, mutational epitope inactivation, T ‐cell receptor antagonism and infection of immunologically privileged tissues. However, these pathways become apparent only in the setting of an ineffective cellular immune response, which is therefore the fundamental underlying cause. Understanding the cellular and molecular mechanisms by which HBV evades host immune responses will eventually help develop new immunotherapeutic strategies designed to terminate chronic HBV infection. The adaptive immune response, particularly the virus-specific CD8(+) T-cell response, is largely responsible for viral clearance and disease pathogenesis during hepatitis B virus (HBV) infection. The HBV-specific CD8(+) T-cell response is vigorous, polyclonal and multispecific in acutely infected patients who successfully clear the virus and relatively weak and narrowly focused in chronically infected patients. The immunological basis for this dichotomy is unclear. A recent study using HBV transgenic mice and HBV-specific T-cell receptor transgenic mice suggests that intrahepatic antigen presentation by HBV positive hepatocytes suppresses HBV-specific CD8(+) T-cell responses through a co-inhibitory molecule, programmed cell death 1 (PD-1). In contrast, antigen presentation by activated professional antigen-presenting cells induces functional differentiation of HBV-specific CD8(+) T cells. These findings suggest that the outcome of T-cell priming is largely dependent on the nature of antigen-presenting cells. Another study suggests that the timing of HBV-specific CD4(+) T-cell priming regulates the magnitude of the HBV-specific CD8(+) T-cell response. Other factors that could regulate HBV-specific cellular immune responses are high viral loads, mutational epitope inactivation, T-cell receptor antagonism and infection of immunologically privileged tissues. However, these pathways become apparent only in the setting of an ineffective cellular immune response, which is therefore the fundamental underlying cause. Understanding the cellular and molecular mechanisms by which HBV evades host immune responses will eventually help develop new immunotherapeutic strategies designed to terminate chronic HBV infection. |
| Author | Isogawa, Masanori Tanaka, Yasuhito |
| Author_xml | – sequence: 1 givenname: Masanori surname: Isogawa fullname: Isogawa, Masanori organization: Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Science, Nagoya, Japan – sequence: 2 givenname: Yasuhito surname: Tanaka fullname: Tanaka, Yasuhito email: ytanaka@med.nagoya-cu.ac.jp organization: Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Science, Nagoya, Japan |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25331910$$D View this record in MEDLINE/PubMed |
| BookMark | eNp9kEtPwzAQhC1URMvjwg9AOSJEwI4TOznSiqfKQwhUxMWyExsMSVzsBOi_xyUtB4TYy-7hm9HOrINebWoJwDaCB8jP4bOc2gMUxThbAQOU0iiEOH7o-RunJCQ4Jn2w7twLhIjCKF4D_SjBGGUIDsD-eVW1tRHalOZpFhgVeDfe6Ea7YBi8a9u6QNdK5o029SZYVbx0cmuxN8D9yfHd6CwcX5-ej47GYY4zlIVxouJU8RRzkWUQCeSPXCRKEVFE_oEkzlNcUEEhhByLlEIikBQyJzRDBVZ4A-x2vlNr3lrpGlZpl8uy5LU0rWOIJD6tD0E8urNAW1HJgk2trridsWVCD8AOyK1xzkrFct3weZrGcl0yBNm8RDYvkX2X6CV7vyRL1z9h1MEfupSzf0h2dnxzu9SEnUa7Rn7-aLh9ZYRimrDJ1Sm7uKTx4-VkyDD-AkhikA8 |
| CitedBy_id | crossref_primary_10_1111_hepr_13472 crossref_primary_10_1186_s12876_019_1004_2 crossref_primary_10_3390_vaccines10020257 crossref_primary_10_1136_jitc_2020_001377 crossref_primary_10_1038_cmi_2016_4 crossref_primary_10_1111_hepr_13952 crossref_primary_10_1152_ajpgi_00064_2019 crossref_primary_10_1038_s41598_018_31065_6 crossref_primary_10_14218_JCTH_2021_00209 crossref_primary_10_3389_fimmu_2021_721975 crossref_primary_10_1089_vim_2015_0079 crossref_primary_10_1098_rspb_2020_2715 crossref_primary_10_1016_j_intimp_2022_108982 crossref_primary_10_1021_acs_jmedchem_6b01442 crossref_primary_10_2217_fvl_2018_0164 crossref_primary_10_1097_MD_0000000000003405 crossref_primary_10_1016_j_antiviral_2020_104816 crossref_primary_10_1097_MD_0000000000008219 crossref_primary_10_1016_j_alcohol_2020_05_002 crossref_primary_10_12677_ACM_2022_122151 crossref_primary_10_1007_s10096_015_2464_0 crossref_primary_10_4254_wjh_v7_i30_2980 crossref_primary_10_1002_jmv_25612 crossref_primary_10_1111_hepr_12513 crossref_primary_10_3390_ijms24087651 crossref_primary_10_1128_JVI_00920_18 crossref_primary_10_1002_jmv_24350 crossref_primary_10_1002_jmv_25265 crossref_primary_10_1055_s_0041_1731708 crossref_primary_10_1186_s12879_019_3853_2 crossref_primary_10_1007_s00705_021_05062_6 crossref_primary_10_1016_j_cyto_2024_156818 crossref_primary_10_1155_2018_1020925 crossref_primary_10_14218_JCTH_2016_00019 crossref_primary_10_3389_fimmu_2022_847105 crossref_primary_10_5633_amm_2017_0408 |
| Cites_doi | 10.1172/JCI200113787 10.1073/pnas.0504273102 10.1084/jem.183.4.1917 10.1111/j.1365-2249.2011.04445.x 10.1038/82161 10.1128/JVI.76.7.3570-3574.2002 10.1016/S1473-3099(11)70314-0 10.1016/j.immuni.2005.05.005 10.1038/32588 10.1038/nm.2811 10.1053/j.gastro.2008.10.048 10.1093/infdis/jit561 10.1084/jem.20061287 10.1128/JVI.77.1.68-76.2003 10.1128/JVI.78.9.4566-4572.2004 10.1016/j.jhep.2010.07.009 10.1126/science.3491425 10.1146/annurev.pathol.1.110304.100230 10.1002/jmv.1890230310 10.1128/CMR.14.4.778-809.2001 10.1002/hep.26938 10.1146/annurev.immunol.20.100101.151926 10.1056/NEJMra031087 10.1073/pnas.0406282101 10.4049/jimmunol.166.9.5430 10.1136/gut.37.4.568 10.1007/s00535-010-0331-4 10.4049/jimmunol.1303432 10.1002/hep.23273 10.4049/jimmunol.153.2.482 10.1128/JVI.79.15.9369-9380.2005 10.1371/journal.ppat.1003490 10.1016/S1074-7613(02)00305-9 10.1038/mtna.2013.43 10.1016/j.jhep.2010.12.031 10.1371/journal.pone.0049135 10.1016/S0002-9440(10)64980-2 10.1128/JVI.79.11.7269-7272.2005 10.1073/pnas.0308340100 10.1016/S0092-8674(00)80952-6 10.4049/jimmunol.177.1.739 10.1016/0092-8674(82)90157-X 10.1038/281646a0 10.1016/S0140-6736(86)90829-9 10.1371/journal.ppat.1002594 10.1136/gut.2008.163600 10.4049/jimmunol.158.12.5692 10.1128/JVI.79.5.3016-3027.2005 10.4049/jimmunol.145.10.3442 10.1002/hep.21345 10.1126/science.284.5415.825 10.1016/S1074-7613(00)80295-2 10.1084/jem.20121172 10.1093/infdis/163.3.454 10.1084/jem.192.7.921 10.1073/pnas.0401771101 10.1084/jem.20011723 10.1146/annurev.immunol.23.021704.115825 10.1128/JVI.01022-08 10.1016/j.jhep.2005.11.015 10.1053/j.gastro.2009.05.047 10.1038/ng.348 10.1038/nrc2355 10.1016/j.jhep.2009.12.017 10.1073/pnas.87.17.6599 10.1128/jvi.69.10.6158-6169.1995 10.1002/hep.21249 10.1038/nri981 10.1172/JCI116281 10.1084/jem.191.8.1269 10.1172/JCI118592 10.1073/pnas.202608199 10.1126/science.3865369 10.1016/j.tibtech.2011.04.009 10.1172/JCI115280 10.4049/jimmunol.171.4.1775 10.1002/(SICI)1521-4141(199901)29:01<284::AID-IMMU284>3.0.CO;2-C 10.1038/nri2858 10.1053/jhep.2001.23045 10.1053/j.gastro.2011.06.051 10.1128/JVI.74.9.4165-4173.2000 10.1053/j.gastro.2009.06.054 10.1128/jvi.68.3.2026-2030.1994 10.1371/journal.pone.0047648 10.1084/jem.20072076 10.1128/MMBR.64.1.51-68.2000 10.1128/JVI.00867-09 10.1146/annurev.iy.13.040195.000333 10.1128/JVI.80.7.3532-3540.2006 10.1128/JVI.78.11.5707-5719.2004 10.1128/JVI.76.17.8609-8620.2002 |
| ContentType | Journal Article |
| Copyright | 2014 The Japan Society of Hepatology 2014 The Japan Society of Hepatology. |
| Copyright_xml | – notice: 2014 The Japan Society of Hepatology – notice: 2014 The Japan Society of Hepatology. |
| DBID | BSCLL AAYXX CITATION NPM 7X8 |
| DOI | 10.1111/hepr.12439 |
| DatabaseName | Istex CrossRef PubMed MEDLINE - Academic |
| DatabaseTitle | CrossRef PubMed MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic CrossRef PubMed |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1872-034X |
| EndPage | 189 |
| ExternalDocumentID | 25331910 10_1111_hepr_12439 HEPR12439 ark_67375_WNG_JM74ZMWB_3 |
| Genre | reviewArticle Journal Article |
| GrantInformation_xml | – fundername: Ministry of Health, Labor and Welfare of Japan – fundername: Ministry of Education, Culture, Sports, Science and Technology, Japan |
| GroupedDBID | --- --K .3N .GA .Y3 05W 0R~ 10A 1B1 1OC 1~5 29I 31~ 33P 3SF 4.4 4G. 50Y 50Z 51W 51X 52M 52N 52O 52P 52R 52S 52T 52U 52V 52W 52X 53G 5GY 5HH 5LA 5VS 66C 7-5 702 7PT 8-0 8-1 8-3 8-4 8-5 8UM 930 A01 A03 AAEDT AAESR AAEVG AAHHS AALRI AANLZ AAONW AAQFI AAQXK AASGY AAXRX AAXUO AAZKR ABCQN ABCUV ABDBF ABEML ABIJN ABJNI ABPVW ABQWH ABXGK ACAHQ ACBWZ ACCFJ ACCZN ACGFO ACGFS ACGOF ACIUM ACMXC ACPOU ACPRK ACSCC ACXBN ACXQS ADBBV ADBTR ADEOM ADIZJ ADKYN ADMGS ADMUD ADOZA ADXAS ADZMN ADZOD AEEZP AEGXH AEIGN AEIMD AENEX AEQDE AEUQT AEUYR AFBPY AFFPM AFGKR AFPWT AFZJQ AHBTC AIACR AIAGR AITUG AITYG AIURR AIWBW AJBDE ALAGY ALMA_UNASSIGNED_HOLDINGS ALUQN AMBMR AMYDB ASPBG ATUGU AVWKF AZBYB AZFZN AZVAB BAFTC BDRZF BFHJK BHBCM BMXJE BROTX BRXPI BSCLL BY8 C45 CAG COF CS3 D-6 D-7 D-E D-F DCZOG DPXWK DR2 DRFUL DRMAN DRSTM DU5 EBD EBS EJD ESX EX3 F00 F01 F04 F5P FDB FEDTE FGOYB FUBAC G-Q G-S G.N GODZA H.X HF~ HGLYW HVGLF HZ~ IHE IX1 J0M K48 KBYEO LATKE LC2 LC3 LEEKS LH4 LITHE LOXES LP6 LP7 LUTES LW6 LYRES M41 MEWTI MK4 MRFUL MRMAN MRSTM MSFUL MSMAN MSSTM MXFUL MXMAN MXSTM N04 N05 N9A NF~ NQ- O66 O9- OIG OVD P2P P2W P2X P2Z P4B P4D Q.N Q11 QB0 R.K R2- RIG ROL RPZ RX1 SEW SSZ SUPJJ TEORI TUS UB1 UHS V8K W8V W99 WBKPD WHWMO WIH WIJ WIK WOHZO WOW WQJ WRC WVDHM WXI WXSBR XG1 ZZTAW ~IA ~WT AAHQN AAIPD AAMNL AANHP AAYCA ABWVN ACRPL ACUHS ACYXJ ADNMO AFWVQ ALVPJ AAYXX ACVFH ADCNI AEUPX AEYWJ AFPUW AGHNM AGQPQ AGYGG AIGII CITATION AAMMB AEFGJ AGXDD AIDQK AIDYY NPM 7X8 |
| ID | FETCH-LOGICAL-c3919-45f48fa83ab9901b13abcb5ff6bd202454c83d7b7000a3b8706b1ebec6791d3f3 |
| IEDL.DBID | DR2 |
| ISSN | 1386-6346 |
| IngestDate | Fri Jul 11 06:30:22 EDT 2025 Mon Jul 21 06:06:59 EDT 2025 Tue Jul 01 01:58:14 EDT 2025 Thu Apr 24 23:10:50 EDT 2025 Wed Jan 22 16:53:07 EST 2025 Wed Oct 30 09:52:12 EDT 2024 |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 2 |
| Keywords | T cells immune response hepatitis B virus immunological priming immunotherapy |
| Language | English |
| License | http://onlinelibrary.wiley.com/termsAndConditions#vor 2014 The Japan Society of Hepatology. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c3919-45f48fa83ab9901b13abcb5ff6bd202454c83d7b7000a3b8706b1ebec6791d3f3 |
| Notes | Ministry of Health, Labor and Welfare of Japan istex:E1F95FF8CED7B6A047E331FCA7BD9929148C3251 ArticleID:HEPR12439 ark:/67375/WNG-JM74ZMWB-3 Ministry of Education, Culture, Sports, Science and Technology, Japan ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| PMID | 25331910 |
| PQID | 1652432536 |
| PQPubID | 23479 |
| PageCount | 11 |
| ParticipantIDs | proquest_miscellaneous_1652432536 pubmed_primary_25331910 crossref_citationtrail_10_1111_hepr_12439 crossref_primary_10_1111_hepr_12439 wiley_primary_10_1111_hepr_12439_HEPR12439 istex_primary_ark_67375_WNG_JM74ZMWB_3 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | February 2015 |
| PublicationDateYYYYMMDD | 2015-02-01 |
| PublicationDate_xml | – month: 02 year: 2015 text: February 2015 |
| PublicationDecade | 2010 |
| PublicationPlace | Netherlands |
| PublicationPlace_xml | – name: Netherlands |
| PublicationTitle | Hepatology research |
| PublicationTitleAlternate | Hepatol Res |
| PublicationYear | 2015 |
| Publisher | Blackwell Publishing Ltd |
| Publisher_xml | – name: Blackwell Publishing Ltd |
| References | Das A, Hoare M, Davies N et al. Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection. J Exp Med 2008; 205: 2111-2124. Su A, Pezacki J, Wodicka L et al. Genomic analysis of the host response to hepatitis C virus infection. Proc Natl Acad Sci U S A 2002; 99: 15669-15674. Zoulim F, Saputelli J, Seeger C. Woodchuck hepatitis virus X protein is required for viral infection in vivo. J Virol 1994; 68: 2026-2030. Wieland SF, Eustaquio A, Whitten-Bauer C, Boyd B, Chisari FV. Interferon prevents formation of replication-competent hepatitis B virus RNA-containing nucleocapsids. Proc Natl Acad Sci U S A 2005; 102: 9913-9917. Zeissig S, Murata K, Sweet L et al. Hepatitis B virus-induced lipid alterations contribute to natural killer T cell-dependent protective immunity. Nat Med 2012; 18: 1060-1068. Guy CS, Mulrooney-Cousins PM, Churchill ND, Michalak TI. Intrahepatic expression of genes affiliated with innate and adaptive immune responses immediately after invasion and during acute infection with woodchuck hepadnavirus. J Virol 2008; 82: 8579-8591. Kong X, Sun R, Chen Y, Wei H, Tian Z. T cells drive myeloid-derived suppressor cell-mediated CD8+ T cell exhaustion in hepatitis B virus-induced immunotolerance. J Immunol 2014; 193: 1645-1653. Baron JL, Gardiner L, Nishimura S, Shinkai K, Locksley R, Ganem D. Activation of a nonclassical NKT cell subset in a transgenic mouse model of hepatitis B virus infection. Immunity 2002; 16: 583-594. Chen M, Billaud J, Sallberg M et al. A function of the hepatitis B virus precore protein is to regulate the immune response to the core antigen. Proc Natl Acad Sci U S A 2004; 101: 14913-14918. Nebbia G, Peppa D, Schurich A et al. Upregulation of the Tim-3/galectin-9 pathway of T cell exhaustion in chronic hepatitis B virus infection. PLoS ONE 2012; 7: e47648. Nakamoto Y, Guidotti L, Pasquetto V, Schreiber R, Chisari F. Differential target cell sensitivity to CTL-activated death pathways in hepatitis B virus transgenic mice. J Immunol 1997; 158: 5692-5697. Kakimi K, Guidotti LG, Koezuka Y, Chisari FV. Natural killer T cell activation inhibits hepatitis B virus replication in vivo. J Exp Med 2000; 192: 921-930. Guidotti LG, Rochford R, Chung J, Shapiro M, Purcell R, Chisari FV. Viral clearance without destruction of infected cells during acute HBV infection. Science 1999; 284: 825-829. Ganem D, Prince AM. Hepatitis B virus infection - natural history and clinical consequences. N Engl J Med 2004; 350: 1118-1129. Fisicaro P, Valdatta C, Boni C et al. Early kinetics of innate and adaptive immune responses during hepatitis B virus infection. Gut 2009; 58: 974-982. Thomson AW, Knolle PA. Antigen-presenting cell function in the tolerogenic liver environment. Nat Rev Immunol 2010; 10: 753-766. Maini MK, Schurich A. The molecular basis of the failed immune response in chronic HBV: therapeutic implications. J Hepatol 2010; 52: 616-619. Isogawa M, Robek MD, Furuichi Y, Chisari FV. Toll-like receptor signaling inhibits hepatitis B virus replication in vivo. J Virol 2005; 79: 7269-7272. Koh S, Shimasaki N, Suwanarusk R et al. A practical approach to immunotherapy of hepatocellular carcinoma using T cells redirected against hepatitis B virus. Mol Ther Nucleic Acids 2013; 2: e114. Ozasa A, Tanaka Y, Orito E et al. Influence of genotypes and precore mutations on fulminant or chronic outcome of acute hepatitis B virus infection. Hepatology 2006; 44: 326-334. Yoo JY, Howard R, Waggoner JG, Hoofnagle JH. Peroxidase-anti-peroxidase detection of hepatitis B surface and core antigen in liver biopsy specimens from patients with chronic type B hepatitis. J Med Virol 1987; 23: 273-281. Castellino F, Germain R. Cooperation between CD4+ and CD8+ T cells: when, where, and how. Annu Rev Immunol 2006; 24: 519-540. Robek MD, Wieland SF, Chisari FV. Inhibition of hepatitis B virus replication by interferon requires proteasome activity. J Virol 2002; 76: 3570-3574. Lanzavecchia A, Lezzi G, Viola A. From TCR engagement to T cell activation: a kinetic view of T cell behavior. Cell 1999; 96: 1-4. Isogawa M, Furuichi Y, Chisari FV. Oscillating CD8(+) T cell effector functions after antigen recognition in the liver. Immunity 2005; 23: 53-63. Michel M-L, Deng Q, Mancini-Bourgine M. Therapeutic vaccines and immune-based therapies for the treatment of chronic hepatitis B: perspectives and challenges. J Hepatol 2011; 54: 1286-1296. Park TS, Rosenberg SA, Morgan RA. Treating cancer with genetically engineered T cells. Trends Biotechnol 2011; 29: 550-557. Chen M, Sällberg M, Hughes J et al. Immune tolerance split between hepatitis B virus precore and core proteins. J Virol 2005; 79: 3016-3027. Milich D, McLachlan A. The nucleocapsid of hepatitis B virus is both a T-cell-independent and a T-cell-dependent antigen. Science 1986; 234: 1398-1401. Ehata T, Omata M, Chuang WL et al. Mutations in core nucleotide sequence of hepatitis B virus correlate with fulminant and severe hepatitis. J Clin Invest 1993; 91: 1206-1213. Reignat S, Webster GJM, Brown D et al. Escaping high viral load exhaustion: CD8 cells with altered tetramer binding in chronic hepatitis B virus infection. J Exp Med 2002; 195: 1089-1101. Dunn C, Peppa D, Khanna P et al. Temporal analysis of early immune responses in patients with acute hepatitis B virus infection. Gastroenterology 2009; 137: 1289-1300. Peppa D, Gill US, Reynolds G et al. Up-regulation of a death receptor renders antiviral T cells susceptible to NK cell-mediated deletion. J Exp Med 2013; 210: 99-114. Hadler SC, Judson FN, O'Malley PM et al. Outcome of hepatitis B virus infection in homosexual men and its relation to prior human immunodeficiency virus infection. J Infect Dis 1991; 163: 454-459. Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer 2008; 8: 299-308. Chisari FV, Pinkert CA, Milich DR et al. A transgenic mouse model of the chronic hepatitis B surface antigen carrier state. Science 1985; 230: 1157-1160. Sugiyama M, Tanaka Y, Kurbanov F et al. Direct cytopathic effects of particular hepatitis B virus genotypes in severe combined immunodeficiency transgenic with urokinase-type plasminogen activator mouse with human hepatocytes. Gastroenterology 2009; 136: 652-662. Boettler T, Panther E, Bengsch B et al. Expression of the interleukin-7 receptor alpha chain (CD127) on virus-specific CD8+ T cells identifies functionally and phenotypically defined memory T cells during acute resolving hepatitis B virus infection. J Virol 2006; 80: 3532-3540. Milich DR, Jones JE, Hughes JL, Price J, Raney AK, McLachlan A. Is a function of the secreted hepatitis B e antigen to induce immunologic tolerance in utero? Proc Natl Acad Sci U S A 1990; 87: 6599-6603. Bertolino P, Bowen DG, McCaughan GW, Fazekas de St Groth B. Antigen-specific primary activation of CD8+ T cells within the liver. J Immunol 2001; 166: 5430-5438. Robek MD, Boyd BS, Wieland SF, Chisari FV. Signal transduction pathways that inhibit hepatitis B virus replication. Proc Natl Acad Sci U S A 2004; 101: 1743-1747. Zhang Z, Protzer U, Hu Z, Jacob J, Liang TJ. Inhibition of cellular proteasome activities enhances hepadnavirus replication in an HBX-dependent manner. J Virol 2004; 78: 4566-4572. Asabe S, Wieland SF, Chattopadhyay PK et al. The size of the viral inoculum contributes to the outcome of hepatitis B virus infection. J Virol 2009; 83: 9652-9662. Sugiyama M, Tanaka Y, Kato T et al. Influence of hepatitis B virus genotypes on the intra- and extracellular expression of viral DNA and antigens. Hepatology 2006; 44: 915-924. Galibert F, Mandart E, Fitoussi F, Tiollais P, Charnay P. Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli. Nature 1979; 281: 646-650. Kamatani Y, Wattanapokayakit S, Ochi H et al. A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians. Nat Genet 2009; 41: 591-595. Zhang Z, Torii N, Hu Z, Jacob J, Liang TJ. X-deficient woodchuck hepatitis virus mutants behave like attenuated viruses and induce protective immunity in vivo. J Clin Invest 2001; 108: 1523-1531. Puoti M, Torti C, Bruno R, Filice G, Carosi G. Natural history of chronic hepatitis B in co-infected patients. J Hepatol 2006; 44: S65-70. Zhang J-Y, Zhang Z, Lin F et al. Interleukin-17-producing CD4+ T cells increase with severity of liver damage in patients with chronic hepatitis B. Hepatology 2009; 51: 81-91. Ando K, Guidotti LG, Cerny A, Ishikawa T, Chisari FV. CTL access to tissue antigen is restricted in vivo. J Immunol 1994; 153: 482-488. Sprent J, Surh CD. T cell memory. Annu Rev Immunol 2002; 20: 551-579. Tjwa ETTL, van Oord GW, Hegmans JP, Janssen HLA, Woltman AM. Viral load reduction improves activation and function of natural killer cells in patients with chronic hepatitis B. J Hepatol 2011; 54: 209-218. Rehermann B, Lau D, Hoofnagle JH, Chisari FV. Cytotoxic T lymphocyte responsiveness after resolution of chronic hepatitis B virus infection. J Clin Invest 1996; 97: 1655-1665. Lunemann S, Malone DFG, Hengst J et al. Compromised function of natural killer cells in acute and chronic viral hepatitis. J Infect Dis 2014; 209: 1362-1373. Chen S, Akbar SMF, Abe M, Hiasa Y, Onji M. Immunosuppressive functions of hepatic myeloid-derived suppressor cells of normal mice and in a murine model of chronic hepatitis B virus. Clin Exp Immunol 2011; 166: 134-142. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998; 392: 245-252. Wieland S, Thimme R, Purcell RH, Chisari FV. Genomic analysis of the host response to hepatitis B virus infection. Proc Natl Acad Sci U S A 2004; 101: 6669-6674. Seeger C, Mason WS. Hepatitis B virus biology. Microbiol Mol Biol Rev 2000; 64: 51-68. Dunn C, Brunetto M, Reynolds G et al. Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage. J Exp Med 2007; 204: 667-680. Kusumoto S, Tanaka Y, Ueda R, Mi 2002; 16 1997; 158 2010; 10 2009; 41 2013; 2 2000; 6 2009; 83 1995; 37 2002; 195 2002; 99 1996; 183 2011; 54 1999; 284 1994; 68 2008; 8 2012; 18 1990; 145 2001; 108 2012; 12 2005; 23 1998; 392 2006; 177 2013; 9 2009; 58 1986; 1 1990; 87 2009; 51 1982; 29 2014; 209 2006; 24 1995; 69 1991; 88 2005; 102 2004; 78 2003; 3 2014; 59 1999; 96 1996; 4 1979; 281 2001; 14 2011; 29 2011; 166 2005; 79 2004; 101 2001; 166 1986; 234 2007; 204 1999; 29 1995; 13 1994; 153 2002; 76 2000; 64 2003; 171 2008; 205 1993; 91 2006; 1 2000; 156 2014; 193 2009; 136 2009; 137 1996; 97 2003; 77 2000; 191 2000; 192 1991; 163 1987; 23 2006; 80 2002; 20 2006; 44 2004; 350 2000; 74 2013; 210 2011; 46 2001; 33 2011; 141 2012; 7 2008; 82 2010; 52 1985; 230 2012; 8 e_1_2_10_23_1 e_1_2_10_46_1 e_1_2_10_69_1 e_1_2_10_21_1 e_1_2_10_44_1 e_1_2_10_40_1 e_1_2_10_91_1 e_1_2_10_70_1 e_1_2_10_2_1 e_1_2_10_72_1 e_1_2_10_18_1 e_1_2_10_74_1 e_1_2_10_53_1 e_1_2_10_6_1 e_1_2_10_16_1 e_1_2_10_39_1 e_1_2_10_76_1 e_1_2_10_55_1 e_1_2_10_8_1 e_1_2_10_14_1 e_1_2_10_37_1 e_1_2_10_57_1 e_1_2_10_78_1 e_1_2_10_58_1 e_1_2_10_13_1 e_1_2_10_34_1 e_1_2_10_11_1 e_1_2_10_32_1 e_1_2_10_30_1 e_1_2_10_51_1 Ferrari C (e_1_2_10_42_1) 1990; 145 e_1_2_10_80_1 e_1_2_10_82_1 e_1_2_10_61_1 e_1_2_10_84_1 e_1_2_10_29_1 e_1_2_10_63_1 e_1_2_10_86_1 e_1_2_10_27_1 e_1_2_10_65_1 e_1_2_10_88_1 e_1_2_10_25_1 e_1_2_10_48_1 e_1_2_10_67_1 e_1_2_10_24_1 e_1_2_10_45_1 e_1_2_10_22_1 e_1_2_10_43_1 Ando K (e_1_2_10_66_1) 1994; 153 e_1_2_10_20_1 e_1_2_10_41_1 Guidotti LG (e_1_2_10_4_1) 1995; 69 e_1_2_10_90_1 e_1_2_10_71_1 e_1_2_10_92_1 e_1_2_10_73_1 e_1_2_10_52_1 e_1_2_10_3_1 e_1_2_10_19_1 e_1_2_10_75_1 e_1_2_10_54_1 e_1_2_10_5_1 e_1_2_10_17_1 e_1_2_10_38_1 Nakamoto Y (e_1_2_10_60_1) 1997; 158 e_1_2_10_77_1 e_1_2_10_56_1 e_1_2_10_79_1 e_1_2_10_7_1 e_1_2_10_15_1 e_1_2_10_36_1 e_1_2_10_12_1 e_1_2_10_35_1 e_1_2_10_9_1 e_1_2_10_59_1 e_1_2_10_10_1 e_1_2_10_33_1 e_1_2_10_31_1 e_1_2_10_50_1 e_1_2_10_81_1 e_1_2_10_62_1 e_1_2_10_83_1 e_1_2_10_64_1 e_1_2_10_85_1 e_1_2_10_28_1 e_1_2_10_49_1 e_1_2_10_87_1 e_1_2_10_26_1 e_1_2_10_47_1 e_1_2_10_68_1 e_1_2_10_89_1 |
| References_xml | – reference: Sun C, Fu B, Gao Y et al. TGF-β1 down-regulation of NKG2D/DAP10 and 2B4/SAP expression on human NK cells contributes to HBV persistence. PLoS Pathog 2012; 8: e1002594. – reference: Wieland SF, Guidotti LG, Chisari FV. Intrahepatic induction of alpha/beta interferon eliminates viral RNA-containing capsids in hepatitis B virus transgenic mice. J Virol 2000; 74: 4165-4173. – reference: Valitutti S, Muller S, Dessing M, Lanzavecchia A. Different responses are elicited in cytotoxic T lymphocytes by different levels of T cell receptor occupancy. J Exp Med 1996; 183: 1917-1921. – reference: Seeger C, Mason WS. Hepatitis B virus biology. Microbiol Mol Biol Rev 2000; 64: 51-68. – reference: Tjwa ETTL, van Oord GW, Hegmans JP, Janssen HLA, Woltman AM. Viral load reduction improves activation and function of natural killer cells in patients with chronic hepatitis B. J Hepatol 2011; 54: 209-218. – reference: Stefan F, Wieland FVC. Stealth and cunning: hepatitis B and hepatitis C viruses. J Virol 2005; 79: 9369-9380. – reference: Sugiyama M, Tanaka Y, Kato T et al. Influence of hepatitis B virus genotypes on the intra- and extracellular expression of viral DNA and antigens. Hepatology 2006; 44: 915-924. – reference: Dunn C, Brunetto M, Reynolds G et al. Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage. J Exp Med 2007; 204: 667-680. – reference: Isogawa M, Chung J, Murata Y, Kakimi K, Chisari FV. CD40 activation rescues antiviral CD8+ T cells from PD-1-mediated exhaustion. PLoS Pathog 2013; 9: e1003490. – reference: Lunemann S, Malone DFG, Hengst J et al. Compromised function of natural killer cells in acute and chronic viral hepatitis. J Infect Dis 2014; 209: 1362-1373. – reference: Robek MD, Wieland SF, Chisari FV. Inhibition of hepatitis B virus replication by interferon requires proteasome activity. J Virol 2002; 76: 3570-3574. – reference: Kakimi K, Isogawa M, Chung J, Sette A, Chisari FV. Immunogenicity and tolerogenicity of hepatitis B virus structural and nonstructural proteins: implications for immunotherapy of persistent viral infections. J Virol 2002; 76: 8609-8620. – reference: Fisicaro P, Valdatta C, Boni C et al. Early kinetics of innate and adaptive immune responses during hepatitis B virus infection. Gut 2009; 58: 974-982. – reference: Nakamoto Y, Guidotti L, Pasquetto V, Schreiber R, Chisari F. Differential target cell sensitivity to CTL-activated death pathways in hepatitis B virus transgenic mice. J Immunol 1997; 158: 5692-5697. – reference: Sugiyama M, Tanaka Y, Kurbanov F et al. Direct cytopathic effects of particular hepatitis B virus genotypes in severe combined immunodeficiency transgenic with urokinase-type plasminogen activator mouse with human hepatocytes. Gastroenterology 2009; 136: 652-662. – reference: Kusumoto S, Tanaka Y, Ueda R, Mizokami M. Reactivation of hepatitis B virus following rituximab-plus-steroid combination chemotherapy. J Gastroenterol 2011; 46: 9-16. – reference: Yoo JY, Howard R, Waggoner JG, Hoofnagle JH. Peroxidase-anti-peroxidase detection of hepatitis B surface and core antigen in liver biopsy specimens from patients with chronic type B hepatitis. J Med Virol 1987; 23: 273-281. – reference: Guidotti LG, Ishikawa T, Hobbs MV, Matzke B, Schreiber R, Chisari FV. Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity 1996; 4: 25-36. – reference: Boettler T, Panther E, Bengsch B et al. Expression of the interleukin-7 receptor alpha chain (CD127) on virus-specific CD8+ T cells identifies functionally and phenotypically defined memory T cells during acute resolving hepatitis B virus infection. J Virol 2006; 80: 3532-3540. – reference: Ehata T, Omata M, Chuang WL et al. Mutations in core nucleotide sequence of hepatitis B virus correlate with fulminant and severe hepatitis. J Clin Invest 1993; 91: 1206-1213. – reference: Sprent J, Surh CD. T cell memory. Annu Rev Immunol 2002; 20: 551-579. – reference: Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998; 392: 245-252. – reference: Boni C, Penna A, Ogg GS et al. Lamivudine treatment can overcome cytotoxic T-cell hyporesponsiveness in chronic hepatitis B: new perspectives for immune therapy. Hepatology 2001; 33: 963-971. – reference: Rehermann B, Lau D, Hoofnagle JH, Chisari FV. Cytotoxic T lymphocyte responsiveness after resolution of chronic hepatitis B virus infection. J Clin Invest 1996; 97: 1655-1665. – reference: Summers J, Mason W. Replication of the genome of a hepatitis B - like virus by reverse transcription of an RNA intermediate. Cell 1982; 29: 403-415. – reference: Thomson AW, Knolle PA. Antigen-presenting cell function in the tolerogenic liver environment. Nat Rev Immunol 2010; 10: 753-766. – reference: Xu D, Fu J, Jin L et al. Circulating and liver resident CD4+CD25+ regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B. J Immunol 2006; 177: 739-747. – reference: Chen S, Akbar SMF, Abe M, Hiasa Y, Onji M. Immunosuppressive functions of hepatic myeloid-derived suppressor cells of normal mice and in a murine model of chronic hepatitis B virus. Clin Exp Immunol 2011; 166: 134-142. – reference: Puoti M, Torti C, Bruno R, Filice G, Carosi G. Natural history of chronic hepatitis B in co-infected patients. J Hepatol 2006; 44: S65-70. – reference: Dunn C, Peppa D, Khanna P et al. Temporal analysis of early immune responses in patients with acute hepatitis B virus infection. Gastroenterology 2009; 137: 1289-1300. – reference: Koh S, Shimasaki N, Suwanarusk R et al. A practical approach to immunotherapy of hepatocellular carcinoma using T cells redirected against hepatitis B virus. Mol Ther Nucleic Acids 2013; 2: e114. – reference: Kakimi K, Guidotti LG, Koezuka Y, Chisari FV. Natural killer T cell activation inhibits hepatitis B virus replication in vivo. J Exp Med 2000; 192: 921-930. – reference: Samuel CE. Antiviral actions of interferons. Clin Microbiol Rev 2001; 14: 778-809, table of contents. – reference: Tillmann H, Trautwein C, Walker D et al. Clinical relevance of mutations in the precore genome of the hepatitis B virus. Gut 1995; 37: 568-573. – reference: Zhang J-Y, Zhang Z, Lin F et al. Interleukin-17-producing CD4+ T cells increase with severity of liver damage in patients with chronic hepatitis B. Hepatology 2009; 51: 81-91. – reference: Kamatani Y, Wattanapokayakit S, Ochi H et al. A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians. Nat Genet 2009; 41: 591-595. – reference: Guy CS, Mulrooney-Cousins PM, Churchill ND, Michalak TI. Intrahepatic expression of genes affiliated with innate and adaptive immune responses immediately after invasion and during acute infection with woodchuck hepadnavirus. J Virol 2008; 82: 8579-8591. – reference: Lanzavecchia A, Lezzi G, Viola A. From TCR engagement to T cell activation: a kinetic view of T cell behavior. Cell 1999; 96: 1-4. – reference: Su A, Pezacki J, Wodicka L et al. Genomic analysis of the host response to hepatitis C virus infection. Proc Natl Acad Sci U S A 2002; 99: 15669-15674. – reference: Nebbia G, Peppa D, Schurich A et al. Upregulation of the Tim-3/galectin-9 pathway of T cell exhaustion in chronic hepatitis B virus infection. PLoS ONE 2012; 7: e47648. – reference: Reignat S, Webster GJM, Brown D et al. Escaping high viral load exhaustion: CD8 cells with altered tetramer binding in chronic hepatitis B virus infection. J Exp Med 2002; 195: 1089-1101. – reference: Park TS, Rosenberg SA, Morgan RA. Treating cancer with genetically engineered T cells. Trends Biotechnol 2011; 29: 550-557. – reference: Maini MK, Boni C, Lee CK et al. The role of virus-specific CD8(+) cells in liver damage and viral control during persistent hepatitis B virus infection. J Exp Med 2000; 191: 1269-1280. – reference: Kong X, Sun R, Chen Y, Wei H, Tian Z. T cells drive myeloid-derived suppressor cell-mediated CD8+ T cell exhaustion in hepatitis B virus-induced immunotolerance. J Immunol 2014; 193: 1645-1653. – reference: Alexander GJ, Eddleston AL. Does maternal antibody to core antigen prevent recognition of transplacental transmission of hepatitis-B-virus infection? Lancet 1986; 1: 296-297. – reference: Isogawa M, Furuichi Y, Chisari FV. Oscillating CD8(+) T cell effector functions after antigen recognition in the liver. Immunity 2005; 23: 53-63. – reference: Castellino F, Germain R. Cooperation between CD4+ and CD8+ T cells: when, where, and how. Annu Rev Immunol 2006; 24: 519-540. – reference: Chisari FV. Rous-Whipple Award Lecture. Viruses, immunity, and cancer: lessons from hepatitis B. Am J Pathol 2000; 156: 1-16. – reference: Isogawa M, Robek MD, Furuichi Y, Chisari FV. Toll-like receptor signaling inhibits hepatitis B virus replication in vivo. J Virol 2005; 79: 7269-7272. – reference: Ozasa A, Tanaka Y, Orito E et al. Influence of genotypes and precore mutations on fulminant or chronic outcome of acute hepatitis B virus infection. Hepatology 2006; 44: 326-334. – reference: Oliviero B, Varchetta S, Paudice E et al. Natural killer cell functional dichotomy in chronic hepatitis B and chronic hepatitis C virus infections. Gastroenterology 2009; 137: 1151-1160. – reference: Kenna T, Mason LG, Porcelli SA et al. NKT cells from normal and tumor-bearing human livers are phenotypically and functionally distinct from murine NKT cells. J Immunol 2003; 171: 1775-1779. – reference: Milich DR, Jones JE, Hughes JL, Price J, Raney AK, McLachlan A. Is a function of the secreted hepatitis B e antigen to induce immunologic tolerance in utero? Proc Natl Acad Sci U S A 1990; 87: 6599-6603. – reference: Galibert F, Mandart E, Fitoussi F, Tiollais P, Charnay P. Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli. Nature 1979; 281: 646-650. – reference: Asabe S, Wieland SF, Chattopadhyay PK et al. The size of the viral inoculum contributes to the outcome of hepatitis B virus infection. J Virol 2009; 83: 9652-9662. – reference: Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer 2008; 8: 299-308. – reference: Zimmermann C, Prevost-Blondel A, Blaser C, Pircher H. Kinetics of the response of naive and memory CD8 T cells to antigen: similarities and differences. Eur J Immunol 1999; 29: 284-290. – reference: Ando K, Guidotti LG, Cerny A, Ishikawa T, Chisari FV. CTL access to tissue antigen is restricted in vivo. J Immunol 1994; 153: 482-488. – reference: Zhang Z, Protzer U, Hu Z, Jacob J, Liang TJ. Inhibition of cellular proteasome activities enhances hepadnavirus replication in an HBX-dependent manner. J Virol 2004; 78: 4566-4572. – reference: Zoulim F, Saputelli J, Seeger C. Woodchuck hepatitis virus X protein is required for viral infection in vivo. J Virol 1994; 68: 2026-2030. – reference: Robek MD, Boyd BS, Wieland SF, Chisari FV. Signal transduction pathways that inhibit hepatitis B virus replication. Proc Natl Acad Sci U S A 2004; 101: 1743-1747. – reference: Michel M-L, Deng Q, Mancini-Bourgine M. Therapeutic vaccines and immune-based therapies for the treatment of chronic hepatitis B: perspectives and challenges. J Hepatol 2011; 54: 1286-1296. – reference: Ferrari C, Bertoletti A, Penna A et al. Identification of immunodominant T cell epitopes of the hepatitis B virus nucleocapsid antigen. J Clin Invest 1991; 88: 214-222. – reference: Crispe I. Hepatic T cells and liver tolerance. Nat Rev Immunol 2003; 3: 51-62. – reference: Zhao J, Li Y, Jin L et al. Natural killer cells are characterized by the concomitantly increased interferon-γ and cytotoxicity in acute resolved hepatitis B patients. PLoS ONE 2012; 7: e49135. – reference: Wieland S, Thimme R, Purcell RH, Chisari FV. Genomic analysis of the host response to hepatitis B virus infection. Proc Natl Acad Sci U S A 2004; 101: 6669-6674. – reference: Chen M, Billaud J, Sallberg M et al. A function of the hepatitis B virus precore protein is to regulate the immune response to the core antigen. Proc Natl Acad Sci U S A 2004; 101: 14913-14918. – reference: Guidotti LG, Rochford R, Chung J, Shapiro M, Purcell R, Chisari FV. Viral clearance without destruction of infected cells during acute HBV infection. Science 1999; 284: 825-829. – reference: Zhang Z, Torii N, Hu Z, Jacob J, Liang TJ. X-deficient woodchuck hepatitis virus mutants behave like attenuated viruses and induce protective immunity in vivo. J Clin Invest 2001; 108: 1523-1531. – reference: Baron JL, Gardiner L, Nishimura S, Shinkai K, Locksley R, Ganem D. Activation of a nonclassical NKT cell subset in a transgenic mouse model of hepatitis B virus infection. Immunity 2002; 16: 583-594. – reference: Chisari FV, Pinkert CA, Milich DR et al. A transgenic mouse model of the chronic hepatitis B surface antigen carrier state. Science 1985; 230: 1157-1160. – reference: Dolina JS, Braciale TJ, Hahn YS. Liver-primed CD8 +T cells suppress antiviral adaptive immunity through galectin-9-independent T-Cell immunoglobulin and mucin 3 engagement of high-mobility group box 1 in mice. Hepatology 2014; 59: 1351-1365. – reference: Ganem D, Prince AM. Hepatitis B virus infection - natural history and clinical consequences. N Engl J Med 2004; 350: 1118-1129. – reference: Wieland SF, Eustaquio A, Whitten-Bauer C, Boyd B, Chisari FV. Interferon prevents formation of replication-competent hepatitis B virus RNA-containing nucleocapsids. Proc Natl Acad Sci U S A 2005; 102: 9913-9917. – reference: Das A, Hoare M, Davies N et al. Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection. J Exp Med 2008; 205: 2111-2124. – reference: Zhang Y, Cobleigh MA, Lian JQ et al. A proinflammatory role for interleukin-22 in the immune response to hepatitis B virus. Gastroenterology 2011; 141: 1897-1906. – reference: Maini MK, Schurich A. The molecular basis of the failed immune response in chronic HBV: therapeutic implications. J Hepatol 2010; 52: 616-619. – reference: Chen M, Sällberg M, Hughes J et al. Immune tolerance split between hepatitis B virus precore and core proteins. J Virol 2005; 79: 3016-3027. – reference: Bertolino P, Bowen DG, McCaughan GW, Fazekas de St Groth B. Antigen-specific primary activation of CD8+ T cells within the liver. J Immunol 2001; 166: 5430-5438. – reference: Gish R, Jia J-D, Locarnini S, Zoulim F. Selection of chronic hepatitis B therapy with high barrier to resistance. Lancet Infect Dis 2012; 12: 341-353. – reference: Zeissig S, Murata K, Sweet L et al. Hepatitis B virus-induced lipid alterations contribute to natural killer T cell-dependent protective immunity. Nat Med 2012; 18: 1060-1068. – reference: Ferrari C, Penna A, Bertoletti A et al. Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection. J Immunol 1990; 145: 3442-3449. – reference: Milich D, McLachlan A. The nucleocapsid of hepatitis B virus is both a T-cell-independent and a T-cell-dependent antigen. Science 1986; 234: 1398-1401. – reference: Guidotti LG, Matzke B, Schaller H, Chisari F. V. High-level hepatitis B virus replication in transgenic mice. J Virol 1995; 69: 6158-6169. – reference: Guidotti LG, Chisari FV. Immunobiology and pathogenesis of viral hepatitis. Annu Rev Pathol 2006; 1: 23-61. – reference: Hadler SC, Judson FN, O'Malley PM et al. Outcome of hepatitis B virus infection in homosexual men and its relation to prior human immunodeficiency virus infection. J Infect Dis 1991; 163: 454-459. – reference: Chisari FV, Ferrari C. Hepatitis B virus immunopathogenesis. Annu Rev Immunol 1995; 13: 29-60. – reference: Limmer A, Ohl J, Kurts C et al. Efficient presentation of exogenous antigen by liver endothelial cells to CD8+ T cells results in antigen-specific T-cell tolerance. Nat Med 2000; 6: 1348-1354. – reference: Thimme R, Wieland S, Steiger C et al. CD8(+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection. J Virol 2003; 77: 68-76. – reference: Peppa D, Gill US, Reynolds G et al. Up-regulation of a death receptor renders antiviral T cells susceptible to NK cell-mediated deletion. J Exp Med 2013; 210: 99-114. – reference: Webster GJM, Reignat S, Brown D et al. Longitudinal analysis of CD8+ T cells specific for structural and nonstructural hepatitis B virus proteins in patients with chronic hepatitis B: implications for immunotherapy. J Virol 2004; 78: 5707-5719. – volume: 44 start-page: 326 year: 2006 end-page: 334 article-title: Influence of genotypes and precore mutations on fulminant or chronic outcome of acute hepatitis B virus infection publication-title: Hepatology – volume: 205 start-page: 2111 year: 2008 end-page: 2124 article-title: Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection publication-title: J Exp Med – volume: 13 start-page: 29 year: 1995 end-page: 60 article-title: Hepatitis B virus immunopathogenesis publication-title: Annu Rev Immunol – volume: 77 start-page: 68 year: 2003 end-page: 76 article-title: CD8(+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection publication-title: J Virol – volume: 64 start-page: 51 year: 2000 end-page: 68 article-title: Hepatitis B virus biology publication-title: Microbiol Mol Biol Rev – volume: 58 start-page: 974 year: 2009 end-page: 982 article-title: Early kinetics of innate and adaptive immune responses during hepatitis B virus infection publication-title: Gut – volume: 209 start-page: 1362 year: 2014 end-page: 1373 article-title: Compromised function of natural killer cells in acute and chronic viral hepatitis publication-title: J Infect Dis – volume: 76 start-page: 3570 year: 2002 end-page: 3574 article-title: Inhibition of hepatitis B virus replication by interferon requires proteasome activity publication-title: J Virol – volume: 33 start-page: 963 year: 2001 end-page: 971 article-title: Lamivudine treatment can overcome cytotoxic T‐cell hyporesponsiveness in chronic hepatitis B: new perspectives for immune therapy publication-title: Hepatology – volume: 234 start-page: 1398 year: 1986 end-page: 1401 article-title: The nucleocapsid of hepatitis B virus is both a T‐cell‐independent and a T‐cell‐dependent antigen publication-title: Science – volume: 12 start-page: 341 year: 2012 end-page: 353 article-title: Selection of chronic hepatitis B therapy with high barrier to resistance publication-title: Lancet Infect Dis – volume: 79 start-page: 3016 year: 2005 end-page: 3027 article-title: Immune tolerance split between hepatitis B virus precore and core proteins publication-title: J Virol – volume: 204 start-page: 667 year: 2007 end-page: 680 article-title: Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell‐mediated liver damage publication-title: J Exp Med – volume: 108 start-page: 1523 year: 2001 end-page: 1531 article-title: X‐deficient woodchuck hepatitis virus mutants behave like attenuated viruses and induce protective immunity in vivo publication-title: J Clin Invest – volume: 24 start-page: 519 year: 2006 end-page: 540 article-title: Cooperation between CD4+ and CD8+ T cells: when, where, and how publication-title: Annu Rev Immunol – volume: 7 start-page: e47648 year: 2012 article-title: Upregulation of the Tim‐3/galectin‐9 pathway of T cell exhaustion in chronic hepatitis B virus infection publication-title: PLoS ONE – volume: 137 start-page: 1289 year: 2009 end-page: 1300 article-title: Temporal analysis of early immune responses in patients with acute hepatitis B virus infection publication-title: Gastroenterology – volume: 158 start-page: 5692 year: 1997 end-page: 5697 article-title: Differential target cell sensitivity to CTL‐activated death pathways in hepatitis B virus transgenic mice publication-title: J Immunol – volume: 153 start-page: 482 year: 1994 end-page: 488 article-title: CTL access to tissue antigen is restricted in vivo publication-title: J Immunol – volume: 195 start-page: 1089 year: 2002 end-page: 1101 article-title: Escaping high viral load exhaustion: CD8 cells with altered tetramer binding in chronic hepatitis B virus infection publication-title: J Exp Med – volume: 29 start-page: 403 year: 1982 end-page: 415 article-title: Replication of the genome of a hepatitis B – like virus by reverse transcription of an RNA intermediate publication-title: Cell – volume: 87 start-page: 6599 year: 1990 end-page: 6603 article-title: Is a function of the secreted hepatitis B e antigen to induce immunologic tolerance in utero? publication-title: Proc Natl Acad Sci U S A – volume: 78 start-page: 4566 year: 2004 end-page: 4572 article-title: Inhibition of cellular proteasome activities enhances hepadnavirus replication in an HBX‐dependent manner publication-title: J Virol – volume: 8 start-page: e1002594 year: 2012 article-title: TGF‐β1 down‐regulation of NKG2D/DAP10 and 2B4/SAP expression on human NK cells contributes to HBV persistence publication-title: PLoS Pathog – volume: 1 start-page: 23 year: 2006 end-page: 61 article-title: Immunobiology and pathogenesis of viral hepatitis publication-title: Annu Rev Pathol – volume: 9 start-page: e1003490 year: 2013 article-title: CD40 activation rescues antiviral CD8+ T cells from PD‐1‐mediated exhaustion publication-title: PLoS Pathog – volume: 74 start-page: 4165 year: 2000 end-page: 4173 article-title: Intrahepatic induction of alpha/beta interferon eliminates viral RNA‐containing capsids in hepatitis B virus transgenic mice publication-title: J Virol – volume: 37 start-page: 568 year: 1995 end-page: 573 article-title: Clinical relevance of mutations in the precore genome of the hepatitis B virus publication-title: Gut – volume: 44 start-page: 915 year: 2006 end-page: 924 article-title: Influence of hepatitis B virus genotypes on the intra‐ and extracellular expression of viral DNA and antigens publication-title: Hepatology – volume: 41 start-page: 591 year: 2009 end-page: 595 article-title: A genome‐wide association study identifies variants in the HLA‐DP locus associated with chronic hepatitis B in Asians publication-title: Nat Genet – volume: 91 start-page: 1206 year: 1993 end-page: 1213 article-title: Mutations in core nucleotide sequence of hepatitis B virus correlate with fulminant and severe hepatitis publication-title: J Clin Invest – volume: 230 start-page: 1157 year: 1985 end-page: 1160 article-title: A transgenic mouse model of the chronic hepatitis B surface antigen carrier state publication-title: Science – volume: 350 start-page: 1118 year: 2004 end-page: 1129 article-title: Hepatitis B virus infection – natural history and clinical consequences publication-title: N Engl J Med – volume: 46 start-page: 9 year: 2011 end-page: 16 article-title: Reactivation of hepatitis B virus following rituximab‐plus‐steroid combination chemotherapy publication-title: J Gastroenterol – volume: 78 start-page: 5707 year: 2004 end-page: 5719 article-title: Longitudinal analysis of CD8+ T cells specific for structural and nonstructural hepatitis B virus proteins in patients with chronic hepatitis B: implications for immunotherapy publication-title: J Virol – volume: 3 start-page: 51 year: 2003 end-page: 62 article-title: Hepatic T cells and liver tolerance publication-title: Nat Rev Immunol – volume: 1 start-page: 296 year: 1986 end-page: 297 article-title: Does maternal antibody to core antigen prevent recognition of transplacental transmission of hepatitis‐B‐virus infection? publication-title: Lancet – volume: 83 start-page: 9652 year: 2009 end-page: 9662 article-title: The size of the viral inoculum contributes to the outcome of hepatitis B virus infection publication-title: J Virol – volume: 99 start-page: 15669 year: 2002 end-page: 15674 article-title: Genomic analysis of the host response to hepatitis C virus infection publication-title: Proc Natl Acad Sci U S A – volume: 96 start-page: 1 year: 1999 end-page: 4 article-title: From TCR engagement to T cell activation: a kinetic view of T cell behavior publication-title: Cell – volume: 8 start-page: 299 year: 2008 end-page: 308 article-title: Adoptive cell transfer: a clinical path to effective cancer immunotherapy publication-title: Nat Rev Cancer – volume: 2 start-page: e114 year: 2013 article-title: A practical approach to immunotherapy of hepatocellular carcinoma using T cells redirected against hepatitis B virus publication-title: Mol Ther Nucleic Acids – volume: 97 start-page: 1655 year: 1996 end-page: 1665 article-title: Cytotoxic T lymphocyte responsiveness after resolution of chronic hepatitis B virus infection publication-title: J Clin Invest – volume: 136 start-page: 652 year: 2009 end-page: 662 article-title: Direct cytopathic effects of particular hepatitis B virus genotypes in severe combined immunodeficiency transgenic with urokinase‐type plasminogen activator mouse with human hepatocytes publication-title: Gastroenterology – volume: 18 start-page: 1060 year: 2012 end-page: 1068 article-title: Hepatitis B virus–induced lipid alterations contribute to natural killer T cell–dependent protective immunity publication-title: Nat Med – volume: 29 start-page: 550 year: 2011 end-page: 557 article-title: Treating cancer with genetically engineered T cells publication-title: Trends Biotechnol – volume: 284 start-page: 825 year: 1999 end-page: 829 article-title: Viral clearance without destruction of infected cells during acute HBV infection publication-title: Science – volume: 166 start-page: 5430 year: 2001 end-page: 5438 article-title: Antigen‐specific primary activation of CD8+ T cells within the liver publication-title: J Immunol – volume: 51 start-page: 81 year: 2009 end-page: 91 article-title: Interleukin‐17‐producing CD4+ T cells increase with severity of liver damage in patients with chronic hepatitis B publication-title: Hepatology – volume: 88 start-page: 214 year: 1991 end-page: 222 article-title: Identification of immunodominant T cell epitopes of the hepatitis B virus nucleocapsid antigen publication-title: J Clin Invest – volume: 14 start-page: 778 year: 2001 end-page: 809 article-title: Antiviral actions of interferons publication-title: Clin Microbiol Rev – volume: 281 start-page: 646 year: 1979 end-page: 650 article-title: Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli publication-title: Nature – volume: 145 start-page: 3442 year: 1990 end-page: 3449 article-title: Cellular immune response to hepatitis B virus‐encoded antigens in acute and chronic hepatitis B virus infection publication-title: J Immunol – volume: 80 start-page: 3532 year: 2006 end-page: 3540 article-title: Expression of the interleukin‐7 receptor alpha chain (CD127) on virus‐specific CD8+ T cells identifies functionally and phenotypically defined memory T cells during acute resolving hepatitis B virus infection publication-title: J Virol – volume: 76 start-page: 8609 year: 2002 end-page: 8620 article-title: Immunogenicity and tolerogenicity of hepatitis B virus structural and nonstructural proteins: implications for immunotherapy of persistent viral infections publication-title: J Virol – volume: 102 start-page: 9913 year: 2005 end-page: 9917 article-title: Interferon prevents formation of replication‐competent hepatitis B virus RNA‐containing nucleocapsids publication-title: Proc Natl Acad Sci U S A – volume: 4 start-page: 25 year: 1996 end-page: 36 article-title: Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes publication-title: Immunity – volume: 156 start-page: 1 year: 2000 end-page: 16 article-title: Rous‐Whipple Award Lecture. Viruses, immunity, and cancer: lessons from hepatitis B publication-title: Am J Pathol – volume: 392 start-page: 245 year: 1998 end-page: 252 article-title: Dendritic cells and the control of immunity publication-title: Nature – volume: 59 start-page: 1351 year: 2014 end-page: 1365 article-title: Liver‐primed CD8 +T cells suppress antiviral adaptive immunity through galectin‐9‐independent T‐Cell immunoglobulin and mucin 3 engagement of high‐mobility group box 1 in mice publication-title: Hepatology – volume: 23 start-page: 273 year: 1987 end-page: 281 article-title: Peroxidase‐anti‐peroxidase detection of hepatitis B surface and core antigen in liver biopsy specimens from patients with chronic type B hepatitis publication-title: J Med Virol – volume: 23 start-page: 53 year: 2005 end-page: 63 article-title: Oscillating CD8(+) T cell effector functions after antigen recognition in the liver publication-title: Immunity – volume: 52 start-page: 616 year: 2010 end-page: 619 article-title: The molecular basis of the failed immune response in chronic HBV: therapeutic implications publication-title: J Hepatol – volume: 7 start-page: e49135 year: 2012 article-title: Natural killer cells are characterized by the concomitantly increased interferon‐γ and cytotoxicity in acute resolved hepatitis B patients publication-title: PLoS ONE – volume: 101 start-page: 6669 year: 2004 end-page: 6674 article-title: Genomic analysis of the host response to hepatitis B virus infection publication-title: Proc Natl Acad Sci U S A – volume: 54 start-page: 1286 year: 2011 end-page: 1296 article-title: Therapeutic vaccines and immune‐based therapies for the treatment of chronic hepatitis B: perspectives and challenges publication-title: J Hepatol – volume: 141 start-page: 1897 year: 2011 end-page: 1906 article-title: A proinflammatory role for interleukin‐22 in the immune response to hepatitis B virus publication-title: Gastroenterology – volume: 79 start-page: 7269 year: 2005 end-page: 7272 article-title: Toll‐like receptor signaling inhibits hepatitis B virus replication in vivo publication-title: J Virol – volume: 16 start-page: 583 year: 2002 end-page: 594 article-title: Activation of a nonclassical NKT cell subset in a transgenic mouse model of hepatitis B virus infection publication-title: Immunity – volume: 29 start-page: 284 year: 1999 end-page: 290 article-title: Kinetics of the response of naive and memory CD8 T cells to antigen: similarities and differences publication-title: Eur J Immunol – volume: 171 start-page: 1775 year: 2003 end-page: 1779 article-title: NKT cells from normal and tumor‐bearing human livers are phenotypically and functionally distinct from murine NKT cells publication-title: J Immunol – volume: 166 start-page: 134 year: 2011 end-page: 142 article-title: Immunosuppressive functions of hepatic myeloid‐derived suppressor cells of normal mice and in a murine model of chronic hepatitis B virus publication-title: Clin Exp Immunol – volume: 193 start-page: 1645 year: 2014 end-page: 1653 article-title: T cells drive myeloid‐derived suppressor cell‐mediated CD8+ T cell exhaustion in hepatitis B virus‐induced immunotolerance publication-title: J Immunol – volume: 163 start-page: 454 year: 1991 end-page: 459 article-title: Outcome of hepatitis B virus infection in homosexual men and its relation to prior human immunodeficiency virus infection publication-title: J Infect Dis – volume: 69 start-page: 6158 year: 1995 end-page: 6169 article-title: V. High‐level hepatitis B virus replication in transgenic mice publication-title: J Virol – volume: 20 start-page: 551 year: 2002 end-page: 579 article-title: T cell memory publication-title: Annu Rev Immunol – volume: 79 start-page: 9369 year: 2005 end-page: 9380 article-title: Stealth and cunning: hepatitis B and hepatitis C viruses publication-title: J Virol – volume: 82 start-page: 8579 year: 2008 end-page: 8591 article-title: Intrahepatic expression of genes affiliated with innate and adaptive immune responses immediately after invasion and during acute infection with woodchuck hepadnavirus publication-title: J Virol – volume: 54 start-page: 209 year: 2011 end-page: 218 article-title: Viral load reduction improves activation and function of natural killer cells in patients with chronic hepatitis B publication-title: J Hepatol – volume: 183 start-page: 1917 year: 1996 end-page: 1921 article-title: Different responses are elicited in cytotoxic T lymphocytes by different levels of T cell receptor occupancy publication-title: J Exp Med – volume: 68 start-page: 2026 year: 1994 end-page: 2030 article-title: Woodchuck hepatitis virus X protein is required for viral infection in vivo publication-title: J Virol – volume: 10 start-page: 753 year: 2010 end-page: 766 article-title: Antigen‐presenting cell function in the tolerogenic liver environment publication-title: Nat Rev Immunol – volume: 6 start-page: 1348 year: 2000 end-page: 1354 article-title: Efficient presentation of exogenous antigen by liver endothelial cells to CD8+ T cells results in antigen‐specific T‐cell tolerance publication-title: Nat Med – volume: 137 start-page: 1151 year: 2009 end-page: 1160 article-title: Natural killer cell functional dichotomy in chronic hepatitis B and chronic hepatitis C virus infections publication-title: Gastroenterology – volume: 191 start-page: 1269 year: 2000 end-page: 1280 article-title: The role of virus‐specific CD8(+) cells in liver damage and viral control during persistent hepatitis B virus infection publication-title: J Exp Med – volume: 101 start-page: 14913 year: 2004 end-page: 14918 article-title: A function of the hepatitis B virus precore protein is to regulate the immune response to the core antigen publication-title: Proc Natl Acad Sci U S A – volume: 101 start-page: 1743 year: 2004 end-page: 1747 article-title: Signal transduction pathways that inhibit hepatitis B virus replication publication-title: Proc Natl Acad Sci U S A – volume: 44 start-page: S65 year: 2006 end-page: 70 article-title: Natural history of chronic hepatitis B in co‐infected patients publication-title: J Hepatol – volume: 177 start-page: 739 year: 2006 end-page: 747 article-title: Circulating and liver resident CD4+CD25+ regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B publication-title: J Immunol – volume: 210 start-page: 99 year: 2013 end-page: 114 article-title: Up‐regulation of a death receptor renders antiviral T cells susceptible to NK cell‐mediated deletion publication-title: J Exp Med – volume: 192 start-page: 921 year: 2000 end-page: 930 article-title: Natural killer T cell activation inhibits hepatitis B virus replication in vivo publication-title: J Exp Med – ident: e_1_2_10_78_1 doi: 10.1172/JCI200113787 – ident: e_1_2_10_56_1 doi: 10.1073/pnas.0504273102 – ident: e_1_2_10_62_1 doi: 10.1084/jem.183.4.1917 – ident: e_1_2_10_86_1 doi: 10.1111/j.1365-2249.2011.04445.x – ident: e_1_2_10_47_1 doi: 10.1038/82161 – ident: e_1_2_10_57_1 doi: 10.1128/JVI.76.7.3570-3574.2002 – ident: e_1_2_10_88_1 doi: 10.1016/S1473-3099(11)70314-0 – ident: e_1_2_10_11_1 doi: 10.1016/j.immuni.2005.05.005 – ident: e_1_2_10_65_1 doi: 10.1038/32588 – ident: e_1_2_10_37_1 doi: 10.1038/nm.2811 – ident: e_1_2_10_5_1 doi: 10.1053/j.gastro.2008.10.048 – ident: e_1_2_10_28_1 doi: 10.1093/infdis/jit561 – ident: e_1_2_10_31_1 doi: 10.1084/jem.20061287 – ident: e_1_2_10_44_1 doi: 10.1128/JVI.77.1.68-76.2003 – ident: e_1_2_10_79_1 doi: 10.1128/JVI.78.9.4566-4572.2004 – ident: e_1_2_10_29_1 doi: 10.1016/j.jhep.2010.07.009 – ident: e_1_2_10_39_1 doi: 10.1126/science.3491425 – ident: e_1_2_10_59_1 doi: 10.1146/annurev.pathol.1.110304.100230 – ident: e_1_2_10_54_1 doi: 10.1002/jmv.1890230310 – ident: e_1_2_10_18_1 doi: 10.1128/CMR.14.4.778-809.2001 – ident: e_1_2_10_81_1 doi: 10.1002/hep.26938 – ident: e_1_2_10_64_1 doi: 10.1146/annurev.immunol.20.100101.151926 – ident: e_1_2_10_2_1 doi: 10.1056/NEJMra031087 – ident: e_1_2_10_14_1 doi: 10.1073/pnas.0406282101 – ident: e_1_2_10_46_1 doi: 10.4049/jimmunol.166.9.5430 – ident: e_1_2_10_73_1 doi: 10.1136/gut.37.4.568 – ident: e_1_2_10_41_1 doi: 10.1007/s00535-010-0331-4 – ident: e_1_2_10_87_1 doi: 10.4049/jimmunol.1303432 – ident: e_1_2_10_49_1 doi: 10.1002/hep.23273 – volume: 153 start-page: 482 year: 1994 ident: e_1_2_10_66_1 article-title: CTL access to tissue antigen is restricted in vivo publication-title: J Immunol doi: 10.4049/jimmunol.153.2.482 – ident: e_1_2_10_19_1 doi: 10.1128/JVI.79.15.9369-9380.2005 – ident: e_1_2_10_12_1 doi: 10.1371/journal.ppat.1003490 – ident: e_1_2_10_36_1 doi: 10.1016/S1074-7613(02)00305-9 – ident: e_1_2_10_92_1 doi: 10.1038/mtna.2013.43 – ident: e_1_2_10_89_1 doi: 10.1016/j.jhep.2010.12.031 – ident: e_1_2_10_27_1 doi: 10.1371/journal.pone.0049135 – ident: e_1_2_10_3_1 doi: 10.1016/S0002-9440(10)64980-2 – ident: e_1_2_10_25_1 doi: 10.1128/JVI.79.11.7269-7272.2005 – ident: e_1_2_10_58_1 doi: 10.1073/pnas.0308340100 – ident: e_1_2_10_61_1 doi: 10.1016/S0092-8674(00)80952-6 – ident: e_1_2_10_85_1 doi: 10.4049/jimmunol.177.1.739 – ident: e_1_2_10_21_1 doi: 10.1016/0092-8674(82)90157-X – ident: e_1_2_10_23_1 doi: 10.1038/281646a0 – ident: e_1_2_10_71_1 doi: 10.1016/S0140-6736(86)90829-9 – ident: e_1_2_10_83_1 doi: 10.1371/journal.ppat.1002594 – ident: e_1_2_10_34_1 doi: 10.1136/gut.2008.163600 – volume: 158 start-page: 5692 year: 1997 ident: e_1_2_10_60_1 article-title: Differential target cell sensitivity to CTL‐activated death pathways in hepatitis B virus transgenic mice publication-title: J Immunol doi: 10.4049/jimmunol.158.12.5692 – ident: e_1_2_10_13_1 doi: 10.1128/JVI.79.5.3016-3027.2005 – volume: 145 start-page: 3442 year: 1990 ident: e_1_2_10_42_1 article-title: Cellular immune response to hepatitis B virus‐encoded antigens in acute and chronic hepatitis B virus infection publication-title: J Immunol doi: 10.4049/jimmunol.145.10.3442 – ident: e_1_2_10_17_1 doi: 10.1002/hep.21345 – ident: e_1_2_10_53_1 doi: 10.1126/science.284.5415.825 – ident: e_1_2_10_55_1 doi: 10.1016/S1074-7613(00)80295-2 – ident: e_1_2_10_32_1 doi: 10.1084/jem.20121172 – ident: e_1_2_10_8_1 doi: 10.1093/infdis/163.3.454 – ident: e_1_2_10_33_1 doi: 10.1084/jem.192.7.921 – ident: e_1_2_10_6_1 doi: 10.1073/pnas.0401771101 – ident: e_1_2_10_76_1 doi: 10.1084/jem.20011723 – ident: e_1_2_10_45_1 doi: 10.1146/annurev.immunol.23.021704.115825 – ident: e_1_2_10_35_1 doi: 10.1128/JVI.01022-08 – ident: e_1_2_10_9_1 doi: 10.1016/j.jhep.2005.11.015 – ident: e_1_2_10_30_1 doi: 10.1053/j.gastro.2009.05.047 – ident: e_1_2_10_48_1 doi: 10.1038/ng.348 – ident: e_1_2_10_90_1 doi: 10.1038/nrc2355 – ident: e_1_2_10_82_1 doi: 10.1016/j.jhep.2009.12.017 – ident: e_1_2_10_70_1 doi: 10.1073/pnas.87.17.6599 – volume: 69 start-page: 6158 year: 1995 ident: e_1_2_10_4_1 article-title: V. High‐level hepatitis B virus replication in transgenic mice publication-title: J Virol doi: 10.1128/jvi.69.10.6158-6169.1995 – ident: e_1_2_10_16_1 doi: 10.1002/hep.21249 – ident: e_1_2_10_67_1 doi: 10.1038/nri981 – ident: e_1_2_10_74_1 doi: 10.1172/JCI116281 – ident: e_1_2_10_52_1 doi: 10.1084/jem.191.8.1269 – ident: e_1_2_10_51_1 doi: 10.1172/JCI118592 – ident: e_1_2_10_20_1 doi: 10.1073/pnas.202608199 – ident: e_1_2_10_72_1 doi: 10.1126/science.3865369 – ident: e_1_2_10_91_1 doi: 10.1016/j.tibtech.2011.04.009 – ident: e_1_2_10_43_1 doi: 10.1172/JCI115280 – ident: e_1_2_10_38_1 doi: 10.4049/jimmunol.171.4.1775 – ident: e_1_2_10_63_1 doi: 10.1002/(SICI)1521-4141(199901)29:01<284::AID-IMMU284>3.0.CO;2-C – ident: e_1_2_10_68_1 doi: 10.1038/nri2858 – ident: e_1_2_10_10_1 doi: 10.1053/jhep.2001.23045 – ident: e_1_2_10_50_1 doi: 10.1053/j.gastro.2011.06.051 – ident: e_1_2_10_24_1 doi: 10.1128/JVI.74.9.4165-4173.2000 – ident: e_1_2_10_26_1 doi: 10.1053/j.gastro.2009.06.054 – ident: e_1_2_10_77_1 doi: 10.1128/jvi.68.3.2026-2030.1994 – ident: e_1_2_10_80_1 doi: 10.1371/journal.pone.0047648 – ident: e_1_2_10_84_1 doi: 10.1084/jem.20072076 – ident: e_1_2_10_22_1 doi: 10.1128/MMBR.64.1.51-68.2000 – ident: e_1_2_10_7_1 doi: 10.1128/JVI.00867-09 – ident: e_1_2_10_40_1 doi: 10.1146/annurev.iy.13.040195.000333 – ident: e_1_2_10_69_1 doi: 10.1128/JVI.80.7.3532-3540.2006 – ident: e_1_2_10_75_1 doi: 10.1128/JVI.78.11.5707-5719.2004 – ident: e_1_2_10_15_1 doi: 10.1128/JVI.76.17.8609-8620.2002 |
| SSID | ssj0017024 |
| Score | 2.2895813 |
| SecondaryResourceType | review_article |
| Snippet | The adaptive immune response, particularly the virus‐specific CD8+ T‐cell response, is largely responsible for viral clearance and disease pathogenesis during... The adaptive immune response, particularly the virus‐specific CD8 + T ‐cell response, is largely responsible for viral clearance and disease pathogenesis... The adaptive immune response, particularly the virus-specific CD8(+) T-cell response, is largely responsible for viral clearance and disease pathogenesis... |
| SourceID | proquest pubmed crossref wiley istex |
| SourceType | Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 179 |
| SubjectTerms | hepatitis B virus immune response immunological priming immunotherapy T cells |
| Title | Immunobiology of hepatitis B virus infection |
| URI | https://api.istex.fr/ark:/67375/WNG-JM74ZMWB-3/fulltext.pdf https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fhepr.12439 https://www.ncbi.nlm.nih.gov/pubmed/25331910 https://www.proquest.com/docview/1652432536 |
| Volume | 45 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3rS8MwED9EQfzi-1FfVBRBsWNtmrQFvzh1zsGGiKIIEpI2xTHpxh4i_vXm-vKBCPqtlEtIcrnLr727XwD2HMcPaRRSLFEOLFewwAo8J7JUlfmCEoTIGNFttVnj1m3e0_sJOC5qYTJ-iPKHG1pG6q_RwIUcfjLyJ9UfVPTpRLB6D5O1EBFdl9xRtlfNb7T1mcWIy3JuUkzj-Wj65TSawoV9_QlqfkWu6dFTn4PHYtBZxkm3Mh7JSvj2jc_xv7Oah9kck5on2SZagAmVLMJ0K4-6L8HRJRaRFHxNZi82dXvcZp2hWTNfOoPx0CySupJluK2f35w2rPyWBSskga31Q2PXj4VPhMQYmbT1QyhpHDMZORiYdUOfRJ70tPMURGJcVNqoeuYFdkRisgKTSS9Ra2AGRMWBhySGytEOOJaOosJ2JENUJ1hkwEGx2jzMKcjxJoxnXnyK4PR5On0DdkvZfka88aPUfqq0UkQMupiq5lF-177gzZbnPrTuapwYsFNolWsDwqiISFRvPOQ2o7onhxJmwGqm7rI3_Va7KLtqwGGqtF9GwhvnV9fp0_pfhDdgRkMwmuWBb8LkaDBWWxrmjOQ2TJ3Uzmr17XRbvwNKwPaW |
| linkProvider | Wiley-Blackwell |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1LT9wwEB7xkEovFFqgaaGkaosEIquNHTvJgUMpj10gqwqBQFyMnTgCUWXRPvrgP_FX-E148iogVKkHDtysaGRN7HnZM_4G4DMhQcySmOET5dDxJA-d0CeJo5s8kIxiiIwZ3ajDW4fezjE7HoHr6i1MgQ9RX7ihZuT2GhUcL6TvaPmZvuw1jHuiYVlTuav__DIntv5ae8Ns7xdCtjYPvrWcsqmAE9PQNeyw1AtSGVCpMCWkXDOIFUtTrhKCeUgvDmjiK9_YCkkVpgGVi3_K_dBNaErNvKMwji3EEap_Y79Gq3L9ZtlDN-AOpx4v0VCxcOgvr_f83zhu5e_Hgtv7sXLu7LZewU21TEWNy0VjOFCN-OoBguSzWccpmCzDbvtroSfTMKKz1_AiKgsL3sBqG9_JVJBUdje1Db-oSed9e93-ed4b9u2qbi2bgcMn4XUWxrJupt-CHVKdhj7iNGpifEyqiGbSJYpj4Cp5YsFytb0iLlHWsdnHD1GdtnC5Rb7cFnyqaS8LbJFHqZZyKalJZO8Cq_F8Jo4622In8r2T6GhdUAs-VmIkjI3AxI_MdHfYFy5nZibCKLdgrpCvejbz1Vhht2nBSi4l_-BEtDa_7-ejd_9DvAgTrYNoT-y1O7vv4aWJOFlR9j4PY4PeUC-YqG6gPuS6ZMPpUwvdLYYVU2k |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1Lb9QwEB6VVqq4FMozQCGIhwQiq40dO_GhB9rtstuyq6qiasXF2ImtVkXZ1T549Df1r_Q_1ZMXFFVIHHrgZkUjazKeVzLjbwBeEpKkLEsZXlEWQaS4CERMssC0eaIYxRQZK7qDIe_tR9uH7HABzuq7MCU-RPPDDS2j8Ndo4OPM_mbkR2Y8abnoREXVUrljfn53H2zT9X7Hne4rQrpbnzZ7QTVTIEipCB03zEaJVQlVGitCOnSLVDNruc4IliGjNKFZrGPnKhTVWAXUIb4oj0WYUUvdvjdgKeJtgYMiOnsNWFUYt6sRugkPOI14BYaKfUO_eL0U_pbwJH9cldteTpWLWNe9Bee1lMoWl5PWfKZb6ekfAJL_ixhvw0qVdPvvSytZhQWT34HlQdVWcBfe9fGWTA1I5Y-s7_hFOzqe-hv-t-PJfOrXXWv5Pdi_Fl7vw2I-ys1D8AU1VsSI0miIizBWE8NUSDTHtFXxzIM39enKtMJYx1EfX2X9rYXiloW4PXjR0I5LZJErqV4XStKQqMkJ9uLFTB4MP8jtQRx9HhxsSOrB81qLpPMQWPZRuRnNpzLkzO1EGOUePCjVq9nNPXU-OGx78LZQkr9wIntbu3vF6tG_ED-D5d1OV37sD3cew02XbrKy5_0JLM4mc7PmUrqZflpYkg9frlvnLgAbb1IY |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Immunobiology+of+hepatitis+B+virus+infection&rft.jtitle=Hepatology+research&rft.au=Isogawa%2C+Masanori&rft.au=Tanaka%2C+Yasuhito&rft.date=2015-02-01&rft.issn=1386-6346&rft.eissn=1872-034X&rft.volume=45&rft.issue=2&rft.spage=179&rft.epage=189&rft_id=info:doi/10.1111%2Fhepr.12439&rft.externalDBID=n%2Fa&rft.externalDocID=10_1111_hepr_12439 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1386-6346&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1386-6346&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1386-6346&client=summon |