title: Inhibition of the HCV core protein on the immune response to HBV surface antigen and on HBV gene expression and replication in vivo.
abstract: The hepatitis C virus (HCV) core protein is a multifunctional protein that can interfere with the induction of an immune response. It has been reported that the HCV core protein inhibits HBV replication in vitro. In this study, we test the effect of the HCV core gene on the priming of the immune response to hepatitis B surface antigen (HBsAg) and on the replication of HBV in vivo. Our results showed that the full-length HCV core gene inhibits the induction of an immune response to the heterogeneous antigen, HBsAg, at the site of inoculation when HCV core (pC191) and HBsAg (pHBsAg) expression plasmids are co-administered as DNA vaccines into BALB/c mice. The observed interference effect of the HCV core occurs in the priming stage and is limited to the DNA form of the HBsAg antigen, but not to the protein form. The HCV core reduces the protective effect of the HBsAg when the HBsAg and the HCV core are co-administered as vaccines in an HBV hydrodynamic mouse model because the HCV core induces immune tolerance to the heterogeneous HBsAg DNA antigen. These results suggest that HCV core may play an important role in viral persistence by the attenuation of host immune responses to different antigens. We further tested whether the HCV core interfered with the priming of the immune response in hepatocytes via the hydrodynamic co-injection of an HBV replication-competent plasmid and an HCV core plasmid. The HCV core inhibited HBV replication and antigen expression in both BALB/c (H-2d) and C57BL/6 (H-2b) mice, the mouse models of acute and chronic hepatitis B virus infections. Thus, the HCV core inhibits the induction of a specific immune response to an HBsAg DNA vaccine. However, HCV C also interferes with HBV gene expression and replication in vivo, as observed in patients with coinfection.
authors.affiliation: State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Zhu
authors.forename: Chunchen
authors.initials: C
authors.lastname: Wu
authors.forename: Wanyu
authors.initials: W
authors.lastname: Deng
authors.forename: Rongjun
authors.initials: R
authors.lastname: Pei
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Cao
authors.forename: Bo
authors.initials: B
authors.lastname: Qin
authors.forename: Mengji
authors.initials: M
authors.lastname: Lu
authors.forename: Xinwen
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006509:Hepatitis B / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D006510:Hepatitis B Antibodies / Q000097:blood / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014779:Virus Replication / Q000276:immunology*
chemical_list: D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus