Are hepatitis B virus "subgenotypes" defined accurately?

Background: Recently, several novel hepatitis B virus (HBV) subgenotypes have been introduced that do not meet proper definition of "subgenotypes". In particular for HBV genotype A, such novel subgenotypes have been reported. Objective: To comprehensively reanalyse all HBV subgenotypes A, and to propose a novel, consistent alternative for HBV classification. Study design: All HBV full-length genome subgenotypes A1-A6 were reanalysed using phylogenetic reconstruction and genetic distance calculation in order to study their evolutionary relationships. Results: Phylogenetic analysis based on the complete genome sequence of subgenotype A strains revealed four distinct clusters supported by high bootstrap values, whereas only the three groups A1, A2 and A6 could be assigned as subgenotypes. Previously introduced subgenotype A3, "tentative A4" and A5 clustered together in one main branch and were designated as "quasi-subgenotypes". Also genetic distances failed to classify these three groups as definite subgenotypes. These results advocate for a new classification of HBV genotype A into subgenotype A1, A2, "quasi-subgenotype A3" and A4. Conclusion: Detailed phylogenetic analysis of the complete genome sequences demonstrates that some of available HBV genotype A strains may not be considered as definite "subgenotypes". These strains, which are mainly of African origin, could be considered as "quasi-subgenotypes"which puts them in between the "clade" and "subgenotype"definition. Geographical origin may have a key role in further classification of HBV subgenotypes. (C) 2010 Published by Elsevier B.V.