Immune Responses in Hepatitis B Virus Infection

Hepatitis B virus infection is one of the most frequent causes of chronic liver disease worldwide. Even though a preventive vaccine is available, the search for a cure for chronically infected patients remains a high priority to reduce the morbidity and mortality from liver cirrhosis and hepatocellular carcinoma. This review summarizes the immune response in acute, self-limited and chronic hepatitis B; its differential effects on viral replication and liver injury; and prospects for immunotherapy.

[1]  F. Hsieh,et al.  Efficacy of Hepatitis B Immune Globulin for Prevention of Perinatal Transmission of the Hepatitis B Virus Carrier State: Final Report of a Randomized Double‐Blind, Placebo‐Controlled Trial , 2007, Hepatology.

[2]  A. Sette,et al.  Immunogenicity and Tolerogenicity of Hepatitis B Virus Structural and Nonstructural Proteins: Implications for Immunotherapy of Persistent Viral Infections , 2002, Journal of Virology.

[3]  C. Biron,et al.  Type I interferons regulate inflammatory cell trafficking and macrophage inflammatory protein 1alpha delivery to the liver. , 2002, The Journal of clinical investigation.

[4]  R. Locksley,et al.  Activation of a nonclassical NKT cell subset in a transgenic mouse model of hepatitis B virus infection. , 2002, Immunity.

[5]  Mark George Thomas,et al.  Resolution of chronic hepatitis B and anti-HBs seroconversion in humans by adoptive transfer of immunity to hepatitis B core antigen. , 2002, Gastroenterology.

[6]  F. Chisari,et al.  Cutting Edge: Inhibition of Hepatitis B Virus Replication by Activated NK T Cells Does Not Require Inflammatory Cell Recruitment to the Liver1 , 2001, The Journal of Immunology.

[7]  G. Ogg,et al.  Lamivudine treatment can overcome cytotoxic T‐cell hyporesponsiveness in chronic hepatitis B: New perspectives for immune therapy , 2001, Hepatology.

[8]  M. Perkus,et al.  DNA prime/canarypox boost—based immunotherapy of chronic hepatitis B virus infection in a chimpanzee , 2001, Hepatology.

[9]  B. Tennant,et al.  Pathogenesis of experimental neonatal woodchuck hepatitis virus infection: Chronicity as an outcome of infection is associated with a diminished acute hepatitis that is temporally deficient for the expression of interferon gamma and tumor necrosis factor‐alpha messenger RNAs , 2001, Hepatology.

[10]  D. Vergani,et al.  Incubation phase of acute hepatitis B in man: Dynamic of cellular immune mechanisms , 2000, Hepatology.

[11]  V. Pasquetto,et al.  Intracellular Hepatitis B Virus Nucleocapsids Survive Cytotoxic T-Lymphocyte-Induced Apoptosis , 2000, Journal of Virology.

[12]  F. Chisari,et al.  Natural Killer T Cell Activation Inhibits Hepatitis B Virus Replication in Vivo , 2000, The Journal of experimental medicine.

[13]  B. Tennant,et al.  Temporal pathogenesis of experimental neonatal woodchuck hepatitis virus infection: Increased initial viral load and decreased severity of acute hepatitis during the development of chronic viral infection , 2000, Hepatology.

[14]  V. Pasquetto,et al.  Host–Virus Interactions during Malaria Infection in Hepatitis B Virus Transgenic Mice , 2000, The Journal of experimental medicine.

[15]  K. Reifenberg,et al.  H-2(d) mice born to and reared by HBeAg-transgenic mothers do not develop T cell tolerance toward the hepatitis B virus core gene products. , 2000, Virology.

[16]  F. Chisari,et al.  Intrahepatic Induction of Alpha/Beta Interferon Eliminates Viral RNA-Containing Capsids in Hepatitis B Virus Transgenic Mice , 2000, Journal of Virology.

[17]  D. Fink,et al.  Cd8+ T Cells Can Block Herpes Simplex Virus Type 1 (HSV-1) Reactivation from Latency in Sensory Neurons , 2000, The Journal of experimental medicine.

[18]  Antonio Bertoletti,et al.  The role of virus-specific CD8(+) cells in liver damage and viral control during persistent hepatitis B virus infection. , 2000 .

[19]  F. Chisari,et al.  Nitric Oxide Inhibits Hepatitis B Virus Replication in the Livers of Transgenic Mice , 2000, The Journal of experimental medicine.

[20]  F. Chisari,et al.  Rous-Whipple Award Lecture. Viruses, immunity, and cancer: lessons from hepatitis B. , 2000, The American journal of pathology.

[21]  K. Matsushima,et al.  Liver-infiltrating T lymphocytes are attracted selectively by IFN-inducible protein-10. , 2000, Cytokine.

[22]  H. Macdonald,et al.  Selective induction of NK cell proliferation and cytotoxicity by activated NKT cells , 2000, European journal of immunology.

[23]  F. Chisari,et al.  Relative Sensitivity of Hepatitis B Virus and Other Hepatotropic Viruses to the Antiviral Effects of Cytokines , 2000, Journal of Virology.

[24]  P. Kloetzel,et al.  Efficient Generation of a Hepatitis B Virus Cytotoxic T Lymphocyte Epitope Requires the Structural Features of Immunoproteasomes , 2000, The Journal of experimental medicine.

[25]  M. Taniguchi,et al.  Augmentation of Vα14 Nkt Cell–Mediated Cytotoxicity by Interleukin 4 in an Autocrine Mechanism Resulting in the Development of Concanavalin a–Induced Hepatitis , 2000, The Journal of experimental medicine.

[26]  D. Adams,et al.  Chemokine and chemokine receptor interactions provide a mechanism for selective T cell recruitment to specific liver compartments within hepatitis C-infected liver. , 1999, Journal of immunology.

[27]  D. Vergani,et al.  Direct ex vivo analysis of hepatitis B virus-specific CD8(+) T cells associated with the control of infection. , 1999, Gastroenterology.

[28]  B. Williams,et al.  The antiviral enzymes PKR and RNase L suppress gene expression from viral and non-viral based vectors. , 1999, Nucleic acids research.

[29]  Kenzo Sato,et al.  Differential expression and regulation of chemokines JE, KC, and IP‐10 gene in primary cultured murine hepatocytes , 1999, Journal of cellular physiology.

[30]  Y. Koezuka,et al.  Cutting edge: Cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. , 1999, Journal of immunology.

[31]  P. Klenerman,et al.  Persistence of lymphocytic choriomeningitis virus at very low levels in immune mice. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[32]  A. Juedes,et al.  Selective retention of activated CD8+ T cells by the normal liver. , 1999, Journal of immunology.

[33]  L. Siracusa,et al.  Hepatitis B virus transgenic mouse model of chronic liver disease , 1999, Nature Medicine.

[34]  F. Chisari,et al.  La Autoantigen Specifically Recognizes a Predicted Stem-Loop in Hepatitis B Virus RNA , 1999, Journal of Virology.

[35]  C. Bréchot,et al.  Specific vaccine therapy in chronic hepatitis B: induction of T cell proliferative responses specific for envelope antigens. , 1999, The Journal of infectious diseases.

[36]  K. Matsushima,et al.  Active participation of CCR5(+)CD8(+) T lymphocytes in the pathogenesis of liver injury in graft-versus-host disease. , 1999, The Journal of clinical investigation.

[37]  F. Chisari,et al.  Noncytopathic Clearance of Lymphocytic Choriomeningitis Virus from the Hepatocyte , 1999, The Journal of experimental medicine.

[38]  M. Shapiro,et al.  Viral clearance without destruction of infected cells during acute HBV infection. , 1999, Science.

[39]  N. Sarvetnick,et al.  Protection from Lethal Coxsackievirus-Induced Pancreatitis by Expression of Gamma Interferon , 1999, Journal of Virology.

[40]  S. Rowland-Jones,et al.  A re-evaluation of the frequency of CD8+ T cells specific for EBV in healthy virus carriers. , 1999, Journal of immunology.

[41]  F. Chisari,et al.  Hepatitis B Virus RNA-Binding Proteins Associated with Cytokine-Induced Clearance of Viral RNA from the Liver of Transgenic Mice , 1999, Journal of Virology.

[42]  J. Altman,et al.  Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function , 1998, The Journal of experimental medicine.

[43]  F. Chisari,et al.  Polyclonality and multispecificity of the CTL response to a single viral epitope. , 1998, Journal of immunology.

[44]  P. Opolon,et al.  Efficient, Repeated Adenovirus-Mediated Gene Transfer in Mice Lacking both Tumor Necrosis Factor Alpha and Lymphotoxin α , 1998, Journal of Virology.

[45]  F. Chisari,et al.  Dendritic cell immunization breaks cytotoxic T lymphocyte tolerance in hepatitis B virus transgenic mice. , 1998, Journal of immunology.

[46]  A. Bertoletti,et al.  Lamivudine treatment can restore T cell responsiveness in chronic hepatitis B. , 1998, The Journal of clinical investigation.

[47]  I. Campbell,et al.  Coxsackievirus B3-induced myocarditis: perforin exacerbates disease, but plays no detectable role in virus clearance. , 1998, The American journal of pathology.

[48]  F. Chisari,et al.  Immune Pathogenesis of Hepatocellular Carcinoma , 1998, The Journal of experimental medicine.

[49]  Polly Matzinger,et al.  A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell , 1998, Nature.

[50]  H. Rammensee,et al.  Protective Immunity Does Not Correlate with the Hierarchy of  Virus-specific Cytotoxic T Cell Responses to Naturally Processed Peptides , 1998, The Journal of experimental medicine.

[51]  R. Zinkernagel,et al.  Induction and Exhaustion of Lymphocytic Choriomeningitis Virus–specific Cytotoxic T Lymphocytes Visualized Using Soluble Tetrameric Major Histocompatibility Complex Class I–Peptide Complexes , 1998, The Journal of experimental medicine.

[52]  G. Kochs,et al.  Mx proteins: mediators of innate resistance to RNA viruses. , 1998, Revue scientifique et technique.

[53]  F. Chisari,et al.  Inhibition of Hepatitis B Virus Replication during Adenovirus and Cytomegalovirus Infections in Transgenic Mice , 1998, Journal of Virology.

[54]  J. Orange,et al.  Early Murine Cytomegalovirus (MCMV) Infection Induces Liver Natural Killer (NK) Cell Inflammation and Protection Through Macrophage Inflammatory Protein 1α (MIP-1α)–dependent Pathways , 1998, The Journal of experimental medicine.

[55]  P. Allavena,et al.  Differential Expression of Chemokine Receptors and Chemotactic Responsiveness of Type 1 T Helper Cells (Th1s) and Th2s , 1998, The Journal of experimental medicine.

[56]  Hiroshi Sato,et al.  CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides. , 1997, Science.

[57]  A. Sette,et al.  Immunological significance of cytotoxic T lymphocyte epitope variants in patients chronically infected by the hepatitis C virus. , 1997, The Journal of clinical investigation.

[58]  H. Thomas,et al.  Heterozygote advantage for HLA class-II type in hepatitis B virus infection , 1997, Nature Genetics.

[59]  V. Pasquetto,et al.  Pathogenetic effector function of CD4-positive T helper 1 cells in hepatitis B virus transgenic mice. , 1997, Journal of immunology.

[60]  F. Su,et al.  Hepatitis B virus HBx protein sensitizes cells to apoptotic killing by tumor necrosis factor alpha. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[61]  H. Grey,et al.  The hepatitis B virus-specific CTL responses induced in humans by lipopeptide vaccination are comparable to those elicited by acute viral infection. , 1997, Journal of immunology.

[62]  H. Yagita,et al.  Impaired induction of cytotoxic T lymphocytes by antagonism of a weak agonist borne by a variant hepatitis C virus epitope , 1997, European journal of immunology.

[63]  A. Lanzavecchia Understanding the Mechanisms of Sustained Signaling and T Cell Activation , 1997, The Journal of experimental medicine.

[64]  F. Chisari,et al.  Interleukin-12 inhibits hepatitis B virus replication in transgenic mice , 1997, Journal of virology.

[65]  G. Geginat,et al.  IFN-gamma is a prerequisite for optimal antigen processing of viral peptides in vivo. , 1997, Journal of immunology.

[66]  Martin A. Nowak,et al.  Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS , 1997, Nature Medicine.

[67]  Xiping Wei,et al.  Antiviral pressure exerted by HIV-l-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus , 1997, Nature Medicine.

[68]  R. Welsh,et al.  Distinct organ-dependent mechanisms for the control of murine cytomegalovirus infection by natural killer cells , 1997, Journal of virology.

[69]  J. Mcghee,et al.  Evidence for CD8+ T-cell immunity to murine rotavirus in the absence of perforin, fas, and gamma interferon , 1997, Journal of virology.

[70]  G. Marinos,et al.  Impact of complete inhibition of viral replication on the cellular immune response in chronic hepatitis B virus infection , 1996, Hepatology.

[71]  G. Riethmüller,et al.  Anergic TH1 clones specific for hepatitis B virus (HBV) core peptides are inhibitory to other HBV core-specific CD4+ T cells in vitro , 1996, Journal of virology.

[72]  R. Welsh,et al.  T-lymphocyte downregulation after acute viral infection is not dependent on CD95 (Fas) receptor-ligand interactions , 1996, Journal of virology.

[73]  H. Davis,et al.  DNA-mediated immunization in a transgenic mouse model of the hepatitis B surface antigen chronic carrier state. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[74]  C. Biron,et al.  NK cell trafficking and cytokine expression in splenic compartments after IFN induction and viral infection. , 1996, Journal of immunology.

[75]  F. Chisari,et al.  The hepatitis B virus persists for decades after patients' recovery from acute viral hepatitis despite active maintenance of a cytotoxic T–lymphocyte response , 1996, Nature Medicine.

[76]  F. Chisari,et al.  Long-lasting memory T cell responses following self-limited acute hepatitis B. , 1996, The Journal of clinical investigation.

[77]  A Sette,et al.  Practical, biochemical and evolutionary implications of the discovery of HLA class I supermotifs. , 1996, Immunology today.

[78]  F. Chisari,et al.  Viral cross talk: intracellular inactivation of the hepatitis B virus during an unrelated viral infection of the liver. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[79]  F. Chisari,et al.  Cytotoxic T lymphocyte responsiveness after resolution of chronic hepatitis B virus infection. , 1996, The Journal of clinical investigation.

[80]  A. Lanzavecchia,et al.  Different responses are elicited in cytotoxic T lymphocytes by different levels of T cell receptor occupancy , 1996, The Journal of experimental medicine.

[81]  M F del Guercio,et al.  Definition of an HLA-A3-like supermotif demonstrates the overlapping peptide-binding repertoires of common HLA molecules. , 1996, Human immunology.

[82]  F. Chisari,et al.  Posttranscriptional clearance of hepatitis B virus RNA by cytotoxic T lymphocyte-activated hepatocytes. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[83]  B. Walker,et al.  HLA class I-restricted cytotoxic T lymphocytes specific for hepatitis C virus. Identification of multiple epitopes and characterization of patterns of cytokine release. , 1995, The Journal of clinical investigation.

[84]  F. Chisari,et al.  High-level hepatitis B virus replication in transgenic mice , 1995, Journal of virology.

[85]  J. Sheridan,et al.  Requirement of MIP-1 alpha for an inflammatory response to viral infection. , 1995, Science.

[86]  M. Schleef,et al.  DNA-mediated immunization to the hepatitis B surface antigen in mice: aspects of the humoral response mimic hepatitis B viral infection in humans. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[87]  U. Spengler,et al.  Activation of a heterogeneous hepatitis B (HB) core and e antigen-specific CD4+ T-cell population during seroconversion to anti-HBe and anti-HBs in hepatitis B virus infection , 1995, Journal of virology.

[88]  J. Yewdell,et al.  CD1 recognition by mouse NK1+ T lymphocytes. , 1995, Science.

[89]  J. Weber,et al.  Naturally occurring variants of human T-cell leukemia virus type I Tax protein impair its recognition by cytotoxic T lymphocytes and the transactivation function of Tax , 1995, Journal of virology.

[90]  F. Chisari,et al.  Breaking tolerance leads to autoantibody production but not autoimmune liver disease in hepatitis B virus envelope transgenic mice. , 1995, Journal of immunology.

[91]  F. Chisari,et al.  Strong, sustained hepatocellular proliferation precedes hepatocarcinogenesis in hepatitis B surface antigen transgenic mice , 1995, Hepatology.

[92]  B. Moss,et al.  The cytotoxic T lymphocyte response to multiple hepatitis B virus polymerase epitopes during and after acute viral hepatitis , 1995, The Journal of experimental medicine.

[93]  G Hermanson,et al.  Binding of a peptide antigen to multiple HLA alleles allows definition of an A2-like supertype. , 1995, Journal of immunology.

[94]  M F del Guercio,et al.  Several HLA alleles share overlapping peptide specificities. , 1995, Journal of immunology.

[95]  A. Vitiello,et al.  The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. , 1994, Journal of immunology.

[96]  N. Hayashi,et al.  Role of Fas ligand in apoptosis induced by hepatitis C virus infection. , 1994, Biochemical and biophysical research communications.

[97]  J. Weber,et al.  The transactivator gene of human T-cell leukemia virus type I is more variable within and between healthy carriers than patients with tropical spastic paraparesis , 1994, Journal of virology.

[98]  A. Sette,et al.  Cytotoxic T lymphocyte response to a wild type hepatitis B virus epitope in patients chronically infected by variant viruses carrying substitutions within the epitope , 1994, The Journal of experimental medicine.

[99]  C. Chu,et al.  Role of hepatitis C and delta viruses in the termination of chronic hepatitis B surface antigen carrier state: a multivariate analysis in a longitudinal follow-up study. , 1994, The Journal of infectious diseases.

[100]  A. Sette,et al.  Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells , 1994, Nature.

[101]  Sarah Rowland-Jones,et al.  Cytotoxic T-cell activity antagonized by naturally occurring HIV-1 Gag variants , 1994, Nature.

[102]  R. Silverman Fascination with 2-5A-dependent RNase: a unique enzyme that functions in interferon action. , 1994, Journal of interferon research.

[103]  Hans Hengartner,et al.  Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice , 1994, Nature.

[104]  F. Chisari,et al.  Class I-restricted cytotoxic T lymphocytes are directly cytopathic for their target cells in vivo. , 1994, Journal of immunology.

[105]  Z. Xiang,et al.  Vaccination with a plasmid vector carrying the rabies virus glycoprotein gene induces protective immunity against rabies virus. , 1994, Virology.

[106]  J. Reimann,et al.  Immunization with soluble hepatitis B virus surface protein elicits murine H-2 class I-restricted CD8+ cytotoxic T lymphocyte responses in vivo. , 1994, Journal of immunology.

[107]  K. Yamamura,et al.  Chronic active hepatitis in transgenic mice expressing interferon-gamma in the liver. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[108]  L. Ferrell,et al.  "Occult" hepatitis B virus as source of infection in liver transplant recipients , 1994, The Lancet.

[109]  V. Srikantan,et al.  DNA inoculation induces neutralizing immune responses against human immunodeficiency virus type 1 in mice and nonhuman primates. , 1993, DNA and cell biology.

[110]  F. Chisari,et al.  Mechanisms of class I restricted immunopathology. A transgenic mouse model of fulminant hepatitis , 1993, The Journal of experimental medicine.

[111]  S. Jonjić,et al.  Participation of endogenous tumour necrosis factor alpha in host resistance to cytomegalovirus infection. , 1993, The Journal of general virology.

[112]  A. Nagler,et al.  Ablation of persistent hepatitis B by bone marrow transplantation from a hepatitis B-immune donor. , 1993, Gastroenterology.

[113]  A. Vitiello,et al.  HLA A2 restricted cytotoxic T lymphocyte responses to multiple hepatitis B surface antigen epitopes during hepatitis B virus infection. , 1993, Journal of immunology.

[114]  C. Biron,et al.  IFN induction and associated changes in splenic leukocyte distribution. , 1993, Journal of immunology.

[115]  Bin Wang,et al.  Gene inoculation generates immune responses against human immunodeficiency virus type 1. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[116]  D. Taub,et al.  Preferential migration of activated CD4+ and CD8+ T cells in response to MIP-1 alpha and MIP-1 beta , 1993, Science.

[117]  A. Vitiello,et al.  Definition of a minimal optimal cytotoxic T-cell epitope within the hepatitis B virus nucleocapsid protein , 1993, Journal of virology.

[118]  J. Ulmer,et al.  Heterologous protection against influenza by injection of DNA encoding a viral protein. , 1993, Science.

[119]  F. Chisari,et al.  HLA-A31- and HLA-Aw68-restricted cytotoxic T cell responses to a single hepatitis B virus nucleocapsid epitope during acute viral hepatitis , 1993, The Journal of experimental medicine.

[120]  H. Dockrell The Cytokine Handbook , 1993 .

[121]  C. Pourcel,et al.  Induction of anti‐hepatitis B surface antigen (HBsAg) antibodies in HBsAg producing transgenic mice: A possible way of circumventing “nonresponse” to HBsAg , 1993, Journal of medical virology.

[122]  W. Greene,et al.  I kappa B/MAD-3 masks the nuclear localization signal of NF-kappa B p65 and requires the transactivation domain to inhibit NF-kappa B p65 DNA binding. , 1992, Molecular biology of the cell.

[123]  S. Ruben,et al.  I kappa B interacts with the nuclear localization sequences of the subunits of NF-kappa B: a mechanism for cytoplasmic retention. , 1992, Genes & development.

[124]  F. Chisari,et al.  Tumor necrosis factor alpha negatively regulates hepatitis B virus gene expression in transgenic mice , 1992, Journal of virology.

[125]  B. Moss,et al.  Hepatitis B virus (HBV)-specific cytotoxic T-cell (CTL) response in humans: characterization of HLA class II-restricted CTLs that recognize endogenously synthesized HBV envelope antigens , 1992, Journal of virology.

[126]  F. Chisari,et al.  HLA class I-restricted human cytotoxic T cells recognize endogenously synthesized hepatitis B virus nucleocapsid antigen. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[127]  J. Wands,et al.  Association of hepatitis B viral precore mutations with fulminant hepatitis B in Japan. , 1991, Virology.

[128]  F. Chisari,et al.  Identification of immunodominant T cell epitopes of the hepatitis B virus nucleocapsid antigen. , 1991, The Journal of clinical investigation.

[129]  J. Wands,et al.  A hepatitis B virus mutant associated with an epidemic of fulminant hepatitis. , 1991, The New England journal of medicine.

[130]  P. Allen,et al.  Separation of IL-4 production from Th cell proliferation by an altered T cell receptor ligand. , 1991, Science.

[131]  A Valli,et al.  Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection. , 1990, Journal of immunology.

[132]  J. Price,et al.  Is a function of the secreted hepatitis B e antigen to induce immunologic tolerance in utero? , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[133]  D. Burns,et al.  Extrahepatic hepatitis B virus DNA sequences in patients with acute hepatitis B infection , 1990, Hepatology.

[134]  F Tsuda,et al.  Hepatitis B viruses with precore region defects prevail in persistently infected hosts along with seroconversion to the antibody against e antigen , 1990, Journal of virology.

[135]  M. Suthanthiran,et al.  A novel addition to the T cell repertory. Cell surface expression of tumor necrosis factor/cachectin by activated normal human T cells , 1990, The Journal of experimental medicine.

[136]  H. Will,et al.  A new hepatitis B virus strain in patients with severe anti-HBe positive chronic hepatitis B. , 1990, Journal of hepatology.

[137]  R. Palmiter,et al.  Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice , 1989, Cell.

[138]  V. Barnaba,et al.  Recognition of hepatitis B virus envelope proteins by liver-infiltrating T lymphocytes in chronic HBV infection. , 1989, Journal of immunology.

[139]  D. Milich T- and B-cell recognition of hepatitis B viral antigens. , 1988, Immunology today.

[140]  R. Palmiter,et al.  Structural and pathological effects of synthesis of hepatitis B virus large envelope polypeptide in transgenic mice. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[141]  F. Chisari,et al.  Intrahepatic, nucleocapsid antigen-specific T cells in chronic active hepatitis B. , 1987, Journal of immunology.

[142]  J. Hoofnagle,et al.  Chronic type B hepatitis and the “healthy” Hbsag carrier state , 1987, Hepatology.

[143]  D. Milich,et al.  The nucleocapsid of hepatitis B virus is both a T-cell-independent and a T-cell-dependent antigen. , 1986, Science.

[144]  J. Summers,et al.  Formation of the pool of covalently closed circular viral DNA in hepadnavirus-infected cells , 1986, Cell.

[145]  V. Desmet,et al.  Interdigitating and dendritic reticulum cells in chronic active hepatitis , 1984, Histopathology.

[146]  A. Dejean,et al.  Detection of hepatitis B virus DNA in pancreas, kidney and skin of two human carriers of the virus. , 1984, The Journal of general virology.

[147]  A. Haase,et al.  Detection of hepatitis B virus DNA in hepatocytes, bile duct epithelium, and vascular elements by in situ hybridization. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[148]  Lu-Yu Hwang,et al.  HEPATOCELLULAR CARCINOMA AND HEPATITIS B VIRUS A Prospective Study of 22 707 Men in Taiwan , 1981, The Lancet.

[149]  Y. Iwakura,et al.  Critical contribution of IFN-gamma and NK cells, but not perforin-mediated cytotoxicity, to anti-metastatic effect of alpha-galactosylceramide. , 2001, European journal of immunology.

[150]  J. Wigginton,et al.  Primary hepatocytes from mice treated with IL-2/IL-12 produce T cell chemoattractant activity that is dependent on monokine induced by IFN-gamma (Mig) and chemokine responsive to gamma-2 (Crg-2). , 2001, Journal of immunology.

[151]  K. Matsushima,et al.  TNF-alpha is a potent inducer for IFN-inducible protein-10 in hepatocytes and unaffected by GM-CSF in vivo, in contrast to IL-1beta and IFN-gamma. , 2000, Cytokine.

[152]  B. Dong,et al.  Alternative function of a protein kinase homology domain in 2', 5'-oligoadenylate dependent RNase L. , 1999, Nucleic acids research.

[153]  R. Andino,et al.  Cytotoxic T-cell immunity to virus-infected non-haematopoietic cells requires presentation of exogenous antigen , 1999, Nature.

[154]  C. Yang,et al.  IFN-gamma is required for viral clearance from central nervous system oligodendroglia. , 1999, Journal of immunology.

[155]  K. Reifenberg,et al.  The hepatitis B virus e antigen cannot pass the murine placenta efficiently and does not induce CTL immune tolerance in H-2b mice in utero. , 1998, Virology.

[156]  L. Lanier NK cell receptors. , 1998, Annual review of immunology.

[157]  C. Samuel,et al.  Reoviruses and the interferon system. , 1998, Current topics in microbiology and immunology.

[158]  D. Hinton,et al.  Mechanisms of viral clearance in perforin-deficient mice. , 1998, Advances in experimental medicine and biology.

[159]  M. Brunda,et al.  Interferons and Other Cytokines , 1997 .

[160]  A. Bertoletti,et al.  Different cytokine profiles of intraphepatic T cells in chronic hepatitis B and hepatitis C virus infections. , 1997, Gastroenterology.

[161]  F. Chisari,et al.  Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. , 1996, Immunity.

[162]  E. Borden,et al.  An overview of the interferon system: signal transduction and mechanisms of action. , 1996, Cancer investigation.

[163]  A. Vitiello,et al.  Development of a lipopeptide-based therapeutic vaccine to treat chronic HBV infection. I. Induction of a primary cytotoxic T lymphocyte response in humans. , 1995, The Journal of clinical investigation.

[164]  F. Chisari,et al.  Hepatitis B virus persistence after recovery from acute viral hepatitis. , 1994, The Journal of clinical investigation.

[165]  M. Grilli,et al.  NF-kappa B and Rel: participants in a multiform transcriptional regulatory system. , 1993, International review of cytology.

[166]  P. Vassalli,et al.  The pathophysiology of tumor necrosis factors. , 1992, Annual review of immunology.

[167]  J. Sung,et al.  Acute exacerbations of chronic type B hepatitis are accompanied by increased T cell responses to hepatitis B core and e antigens. Implications for hepatitis B e antigen seroconversion. , 1992, The Journal of clinical investigation.

[168]  G. B. Thornton,et al.  Antibody production to the nucleocapsid and envelope of the hepatitis B virus primed by a single synthetic T cell site , 1987, Nature.

[169]  J. Hoofnagle,et al.  Acute type A hepatitis during chronic hepatitis B virus infection: Association of depressed hepatitis B virus replication with appearance of endogenous alpha interferon , 1984, Journal of medical virology.