title: HBsAg sT123N mutation induces stronger antibody responses to HBsAg and HBcAg and accelerates in vivo HBsAg clearance.
abstract: Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. Some mutants harboring substitutions to Asn in HBsAg MHR may have an additional potential N-glycosylation site. We have previously showed that sT123N substitution could generate additional N-glycosylated forms of HBsAg. In the present study, 1.3-fold-overlength HBV genomes containing the sT123N substitution were digested from the pHBV1.3-sT123N construct and subcloned into the pAAV vector to generate pAAV1.3-sT123N for hydrodynamic injection (HI) in mice. Viral expression and replication were phenotypically characterized by transient transfection. The results demonstrated that sT123N substitution impaired virion secretion, resulting in intracellular retention of HBcAg. Using the HBV HI mouse model, we found that mice mounted significantly stronger antibody responses to HBsAg and HBcAg, which accelerated HBsAg clearance. Thus, additional N-glycosylation generated by amino acid substitutions in HBsAg MHR may significantly modulate specific host immune responses and influence HBV infection in vivo. Our results help further the understanding of the role of immune escape mutants with N-linked glycosylation in the biology of HBV infection.
authors.affiliation: State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Songxia
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Kaitao
authors.initials: K
authors.lastname: Zhao
authors.affiliation: State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Shuhui
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. Electronic address: wucc@wh.iov.cn.
authors.forename: Chunchen
authors.initials: C
authors.lastname: Wu
authors.affiliation: State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Yongxuan
authors.initials: Y
authors.lastname: Yao
authors.affiliation: State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Cao
authors.affiliation: State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Hu
authors.affiliation: State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Rongjuan
authors.initials: R
authors.lastname: Pei
authors.affiliation: State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; Institute of Virology, University Hospital of Essen, Essen, Germany.
authors.forename: Mengji
authors.initials: M
authors.lastname: Lu
authors.affiliation: State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Xinwen
authors.initials: X
authors.lastname: Chen
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000917:Antibody Formation; D004195:Disease Models, Animal; D006509:Hepatitis B / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000097:blood*; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000235:genetics* / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D020125:Mutation, Missense
chemical_list: D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens
keywords: Hepatitis B virus; Immune escape mutants; Immune responses; N-glycosylation; Viral clearance