Clinical Implications of Evolutionary Patterns of Homologous, Full- Length Hepatitis B Virus Quasispecies in Different Hosts after Perinatal Infection

Chronic hepatitis B virus (HBV) infection via perinatal transmission is common in the Asia-Pacific region, but related quasispe-cies (QS) characteristics are not yet defined. To investigate the homologous, full-length HBVQS 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 HBVwere amplified by PCR from se-rum 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 HBVwere similar betweenmothers and daughters (median of 0.9734 compared to 0.9688, P> 0.05), as were the diversities (median of 3.396 103 compared to 4.617 103substitutions/site, P> 0.05). How-ever, 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 im-mune phases or stages. The nucleotide substitution rate of full-length HBVwas 14.388 105 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 nu-merically comparable full-length QS complexities and diversities. The different patterns may correlate with the immune stages of chronic HBV infection, which warrants further study