After the infection with HBV,the host's antiviral immune response is a key factor for the outcome of infection. At present,it is widely believed that the host's innate immunity and acquired immunity are impaired during chronic HBV infection,because of which HBV clearance cannot be achieved. To achieve a long-lasting immune control of HBV infection,we need to comprehensively understand the mechanisms of dysfunction of innate immune response and specific immune response in chronic HBV infection. This article summarizes the research advances in the immune response mechanism of chronicity of HBV infection.
[1]CUI X,CLARK DN,LIU K,et al.Viral DNA-dependent induction of innate immune response to hepatitis B virus in immortalized mouse hepatocytes[J].J Virol,2016,90(1):486-496.
|
[2]SATO S,LI K,KAMEYAMA T,et al.The RNA sensor RIG-I dually functions as an innate sensor and direct antiviral factor for hepatitis B virus[J].Immunity,2015,42(1):123-132.
|
[3]ZHANG X,MA Z,LIU H,et al.Role of Toll-like receptor 2 in the immune response against hepadnaviral infection[J].J Hepatol,2012,57(3):522-528.
|
[4]ISOGAWA M,ROBEK MD,FURUICHI Y,et al.Toll-like receptor signaling inhibits hepatitis B virus replication in vivo[J].J Virol,2005,79(11):7269-7272.
|
[5]WU J,LU M,MENG Z,et al.Toll-like receptor-mediated control of HBV replication by nonparenchymal liver cells in mice[J].Hepatology,2007,46(6):1769-1778.
|
[6]WU J,HUANG S,ZHAO X,et al.Poly(I∶C)treatment leads to interferon-dependent clearance of hepatitis B virus in a hydrodynamic injection mouse model[J].J Virol,2014,88(18):10421-10431.
|
[7]LAN P,ZHANG C,HAN Q,et al.Therapeutic recovery of hepatitis B virus(HBV)-induced hepatocyte-intrinsic immune defect reverses systemic adaptive immune tolerance[J].Hepatology,2013,58(1):73-85.
|
[8]LANFORD RE,GUERRA B,CHAVEZ D,et al.GS-9620,an oral agonist of Toll-like receptor-7,induces prolonged suppression of hepatitis B virus in chronically infected chimpanzees[J].Gastroenterology,2013,144(7):1508-1517,1517.e1-e10.
|
[9]WU J,MENG Z,JIANG M,et al.Hepatitis B virus suppresses Toll-like receptor-mediated innate immune responses in murine parenchymal and nonparenchymal liver cells[J].Hepatology,2009,49(4):1132-1140.
|
[10]VISVANATHAN K,SKINNER NA,THOMPSON AJ,et al.Regulation of Toll-like receptor-2 expression in chronic hepatitis B by the precore protein[J].Hepatology,2007,45(1):102-110.
|
[11]WANG S,CHEN Z,HU C,et al.Hepatitis B virus surface antigen selectively inhibits TLR2 ligand-induced IL-12 production in monocytes/macrophages by interfering with JNK activation[J].J Immunol,2013,190(10):5142-5151.
|
[12]ZHENG M,SUN R,WEI H,et al.NK cells help induce antihepatitis B virus CD8+T cell immunity in mice[J].J Immunol,2016,196(10):4122-4131.
|
[13]REHERMANN B.Natural killer cells in viral hepatitis[J].Cell Mol Gastroenterol Hepatol,2015,1(6):578-588.
|
[14]PEPPA D,MICCO L,JAVAID A,et al.Blockade of immunosuppressive cytokines restores NK cell antiviral function in chronic hepatitis B virus infection[J].PLo S Pathog,2010,6(12):e1001227.
|
[15]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].J Exp Med,2013,210(1):99-114.
|
[16]KAKIMI K,GUIDOTTI LG,KOEZUKA Y,et al.Natural killer T cell activation inhibits hepatitis B virus replication in vivo[J].J Exp Med,2000,192(7):921-930.
|
[17]ITO H,ANDO K,ISHIKAWA T,et al.Role of Valpha14+NKT cells in the development of Hepatitis B virus-specific CTL:activation of Valpha14+NKT cells promotes the breakage of CTL tolerance[J].Int Immunol,2008,20(7):869-879.
|
[18]ZEISSIG S,MURATA K,SWEET L,et al.Hepatitis B virus-induced lipid alterations contribute to natural killer T cell-dependent protective immunity[J].Nat Med,2012,18(7):1060-1068.
|
[19]JIANG X,ZHANG M,LAI Q,et al.Restored circulating invariant nkt cells are associated with viral control in patients with chronic hepatitis B[J].PLo S One,2011,6(12):69.
|
[20]OP den BROUW ML,BINDA RS,van ROOSMALEN MH,et al.Hepatitis B virus surface antigen impairs myeloid dendritic cell function:a possible immune escape mechanism of hepatitis B virus[J].Immunology,2009,126(2):280-289.
|
[21]CHEN L,ZHANG Z,CHEN W,et al.B7-H1 up-regulation on myeloid dendritic cells significantly suppresses T cell immune function in patients with chronic hepatitis B[J].J Immunol,2007,178(10):6634-6641.
|
[22]ZHANG Z,CHEN D,YAO J,et al.Increased infiltration of intrahepatic DC subsets closely correlate with viral control and liver injury in immune active pediatric patients with chronic hepatitis B[J].Clin Immunol,2007,122(2):173-180.
|
[23]BILITY MT,CHENG L,ZHANG Z,et al.Hepatitis B virus infection and immunopathogenesis in a humanized mouse model:induction of human-specific liver fibrosis and M2-like macrophages[J].PLo S Pathog,2014,10(3):e1004032.
|
[24]XU L,YIN W,SUN R,et al.Kupffer cell-derived IL-10 plays a key role in maintaining humoral immune tolerance in hepatitis B virus-persistent mice[J].Hepatology,2014,59(2):443-452.
|
[25]LI M,SUN R,XU L,et al.Kupffer cells support hepatitis B virus-mediated CD8+T cell exhaustion via hepatitis B core antigenTLR2 interactions in mice[J].J Immunol,2015,195(7):3100-3109.
|
[26]TIAN Y,KUO CF,AKBARI O,et al.Maternal-derived hepatitis B virus e antigen alters macrophage function in offspring to drive viral persistence after vertical transmission[J].Immunity,2016,44(5):1204-1214.
|
[27]THIMME R,WIELAND S,STEIGER C,et al.CD8+T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection[J].J Virol,2003,77(1):68-76.
|
[28]REHERMANN B,FERRARI C,PASQUINELLI C,et al.The hepatitis B virus persists for decades after patients'recovery from acute viral hepatitis despite active maintenance of a cytotoxic Tlymphocyte response[J].Nat Med,1996,2(10):1104-1108.
|
[29]GUIDOTTI LG,INVERSO D,SIRONI L,et al.Immunosurveillance of the liver by intravascular effector CD8(+)T cells[J].Cell,2015,161(3):486-500.
|
[30]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[J].Hepatology,2001,33(4):963-971.
|
[31]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[J].PLo S One,2012,7(10):e47648.
|
[32]SCHURICH A,KHANNA P,LOPES AR,et al.Role of the coinhibitory receptor cytotoxic T lymphocyte antigen-4 on apoptosisprone CD8 T cells in persistent hepatitis B virus infection[J].Hepatology,2011,53(5):1494-1503.
|
[33]BENGSCH B,MARTIN B,THIMME R.Restoration of HBV-specific CD8+T cell function by PD-1 blockade in inactive carrier patients is linked to T cell differentiation[J].J Hepatol,2014,61(6):1212-1219.
|
[34]RAZIORROUH B,SCHRAUT W,GERLACH T,et al.The immunoregulatory role of CD244 in chronic hepatitis B infection and its inhibitory potential on virus-specific CD8+T-cell function[J].Hepatology,2010,52(6):1934-1947.
|
[35]LIU J,ZHANG E,MA Z,et al.Enhancing virus-specific immunity in vivo by combining therapeutic vaccination and PD-l1 blockade in chronic hepadnaviral infection[J].PLo S Pathog,2013,58(1):e1003856.
|
[36]PALLETT LJ,GILL US,QUAGLIA A,et al.Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells[J].Nat Med,2015,21(6):591-600.
|
[37]ASABE S,WIELAND SF,CHATTOPADHYAY PK,et al.The size of the viral inoculum contributes to the outcome of hepatitis B virus infection[J].J Virol,2009,83(19):9652-9662.
|
[38]FRANCO A,GUIDOTTI LG,HOBBS MV,et al.Pathogenetic effector function of CD4-positive T helper 1 cells in hepatitis B virus transgenic mice[J].J Immunol,1997,159(4):2001-2008.
|
[39]PENNA A,FOWLER P,BERTOLETTI A,et al.Hepatitis B virus(HBV)-specific cytotoxic T-cell(CTL)response in humans:characterization of HLA classⅡ-restricted CTLs that recognize endogenously synthesized HBV envelope antigens[J].J Virol,1992,66(2):1193-1198.
|
[40]ZENG Z,LI L,CHEN Y,et al.Interferon-gamma facilitates hepatic antiviral T cell retention for the maintenance of liver-induced systemic tolerance[J].J Exp Med,2016,213(6):1079-1093.
|
[41]DIETZE KK,SCHIMMER S,KRETZMER F,et al.Characterization of the treg response in the hepatitis B virus hydrodynamic injection mouse model[J].PLo S One,2016,11(3):e0151717.
|
[42]YANG B,WANG Y,ZHAO C,et al.Increased Th17 cells and interleukin-17 contribute to immune activation and disease aggravation in patients with chronic hepatitis B virus infection[J].Immunol Lett,2013,149(1-2):41-49.
|
[43]PUBLICOVER J,GOODSELL A,NISHIMURA S,et al.IL-21 is pivotal in determining age-dependent effectiveness of immune responses in a mouse model of human hepatitis B[J].J Clin Invest,2011,121(3):1154-1162.
|
[44]LI Y,MA S,TANG L,et al.Circulating chemokine(C-X-C Motif)receptor 5(+)CD4(+)T cells benefit hepatitis B e antigen seroconversion through IL-21 in patients with chronic hepatitis B virus infection[J].Hepatology,2013,8(4):1277-1286.
|
[45]XU L,YIN W,SUN R,et al.Liver type I regulatory T cells suppress germinal center formation in HBV-tolerant mice[J].Proc Natl Acad Sci U S A,2013,110(42):16993-16998.
|
[46]YAN H,ZHONG G,XU G,et al.Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus[J].Elife,2012,3(1):e00049.
|
[47]ZHANG TY,YUAN Q,ZHAO JH,et al.Prolonged suppression of HBV in mice by a novel antibody that targets a unique epitope on hepatitis B surface antigen[J].Gut,2016,65(4):658-671.
|
[48]OLIVIERO B,CERINO A,VARCHETTA S,et al.Enhanced B-cell differentiation and reduced proliferative capacity in chronic hepatitis C and chronic hepatitis B virus infections[J].J Hepatol,2011,55(1):53-60.
|
[49]DAS A,ELLIS G,PALLANT C,et al.IL-10-producing regulatory B cells in the pathogenesis of chronic hepatitis B virus infection[J].J Immunol,2012,189(8):3925-3935.
|