title: Clinical implications of evolutionary patterns of homologous, full-length hepatitis B virus quasispecies in different hosts after perinatal infection.
abstract: Chronic hepatitis B virus (HBV) infection via perinatal transmission is common in the Asia-Pacific region, but related quasispecies (QS) characteristics are not yet defined. To investigate the homologous, full-length HBV QS after perinatal infection and their clinical implications, five pairs of mother-daughter patients with chronic HBV infection (one patient with liver cirrhosis, one with immune tolerance, and eight with chronic hepatitis) were included. Full-length HBV were amplified by PCR from serum samples before antiviral treatment and cloned; an average of 17 clones per sample were sequenced, and the QS complexities, diversities, and evolution patterns were analyzed. Full-length HBV sequence similarities within mother-daughter pairs were 91.3 to 98.3%. The QS complexities of full-length HBV were similar between mothers and daughters (median of 0.9734 compared to 0.9688, P>0.05), as were the diversities (median of 3.396×10(-3) compared to 4.617×10(-3) substitutions/site, P>0.05). However, the distribution patterns of QS complexities and diversities within specific genes were different, and QS genetic distances of the mothers were higher than those of daughters, both more evident in pairs with different antiviral responses and different immune phases or stages. The nucleotide substitution rate of full-length HBV was 14.388×10(-5) substitutions/site/year, whereas the preC/C gene rate was the highest. Mutations and indels were more common in clones from the mothers, which decreased the affinity of epitopes by 6- to 89-fold. The various genes from homologous HBV genomes evolved in different patterns despite numerically comparable full-length QS complexities and diversities. The different patterns may correlate with the immune stages of chronic HBV infection, which warrants further study.
authors.affiliation: Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: De-Min
authors.initials: DM
authors.lastname: Yu
authors.forename: Su-Yuan
authors.initials: SY
authors.lastname: Huang
authors.forename: Jia-Lun
authors.initials: JL
authors.lastname: Yu
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Zhang
authors.forename: Qi-Ming
authors.initials: QM
authors.lastname: Gong
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000235:genetics; D000939:Epitopes / Q000235:genetics; D005260:Female; D016679:Genome, Viral / Q000235:genetics; D005838:Genotype; D006512:Hepatitis B Core Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000635:transmission* / Q000821:virology; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008875:Middle Aged; D009035:Mothers; D009154:Mutation / Q000235:genetics; D009679:Nuclear Family; D016133:Polymerase Chain Reaction / Q000379:methods; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA / Q000379:methods; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D000939:Epitopes; D006512:Hepatitis B Core Antigens