title: Characterization of Novel Hepatitis B Virus PreS/S-Gene Mutations in a Patient with Occult Hepatitis B Virus Infection.
abstract: The impact of hepatitis B virus (HBV) preS/S-gene mutations on occult HBV infection (OBI) is not fully understood. This study characterized multiple novel HBV preS/S-gene mutants obtained from an OBI patient.
  
  
  
  PreS/S-gene mutants were analyzed by clonal sequencing. Viral replication and expression were analyzed by transfecting HBV genomic recombinants into HepG2 cells.
  
  
  
  Twenty-one preS/S-gene mutants were cloned from four sequential serum samples, including 13 mutants that were not previously documented: (1) sI/T126V+sG145R; (2) preS1 nt 3014-3198 deletion; (3) preS1 nt 3046-3177 deletion; (4) preS1 nt 3046-3177 deletion+s115-116 "INGTST" insertion; (5) preS1 nt 3046-3177 deletion+s115-116 "INGTST" insertion+sG145R; (6) preS1 nt 3115-3123 deletion+sQ129N; (7) preS1 nt 3115-3123 deletion+s126-127 "RPCMNCTI" insertion; (8) s115-116 "INGTST" insertion; (9) s115-116 "INGTST" insertion+sG145R; (10) s126-127 "RPCMNCTI" insertion; (11) preS1 nt 2848-2862 deletion+preS2 initiation codon M→I; (12) s122-123 "KSTGLCK" insertion+sQ129N; and (13) preS2 initiation codon M→I+s131-133TSM→NST. The proportion of preS1 nt 3046-3177 deletion and preS2 initiation codon M→I+s131-133TSM→NST mutants increased in the viral pool with prolonged disease. The 13 novel OBI-related mutants showed a 51.2-99.9% decrease in HBsAg levels compared with that of the wild type. Additional N-glycosylation-associated mutations, sQ129N and s131-133TSM→NST, but not s126-127 "RPCMNCTI," greatly attenuated anti-HBs binding to HBsAg. Compared with the wild type, replication and surface antigen promoter II activity of the preS1 nt 3046-3177 deletion mutant decreased by 43.3% and 97.0%, respectively.
  
  
  
  PreS/S-gene mutations may play coordinated roles in the presentation of OBI and might be associated with disease progression. This has implications for HBV diagnosis and vaccine improvement.
authors.affiliation: Institute of Infectious Diseases/Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Infectious Diseases/Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Infectious Diseases/Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Institute of Infectious Diseases/Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Institute of Infectious Diseases/Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Rongjuan
authors.initials: R
authors.lastname: Chen
authors.affiliation: Institute of Infectious Diseases/Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Si
authors.affiliation: Institute of Infectious Diseases/Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Institute of Infectious Diseases/Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of liver disease, General Hospital of Beijing Military Region, Beijing 100700, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Infectious Diseases/Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Institute of Infectious Diseases/Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of liver disease, General Hospital of Beijing Military Region, Beijing 100700, China.
authors.forename: Juqiang
authors.initials: J
authors.lastname: Han
authors.affiliation: Institute of Infectious Diseases/Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Dongping
authors.initials: D
authors.lastname: Xu
mesh_terms: D045744:Cell Line, Tumor; D004279:DNA, Viral; D015870:Gene Expression; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D006509:Hepatitis B / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D014779:Virus Replication / Q000235:genetics
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens