Abstract
BackgroundMore than ten subgenotypes of genotype C Hepatitis B virus (HBV) have been reported, including C1 to C16 and two C/D recombinant subgenotypes (CD1 and CD2), however, inconsistent designations of these subgenotypes still exist.Methodology/Principal FindingsWe performed a phylogenetic analysis of all full-length genotype C HBV genome sequences to correct the misclassifications of HBV subgenotypes and to study the influence of recombination on HBV subgenotyping. Our results showed that although inclusion of the recombinant sequences changed the topology of the phylogenetic tree, it did not affect the subgenotyping of the non-recombinant sequences, except subgenotype C2. In addition, most of the subgenotypes have been properly designated. However, several misclassifications of HBV subgenotypes have been identified and corrected. For example, C11 proposed by Utsumi and colleagues in 2011 was found to be grouped with C12 proposed by Mulyanto and colleagues. Two sequences, GQ358157 and GU721029, previously designated as C6 have been re-designated as C12 and C7, respectively. Moreover, a quasi-subgenotype C2 was proposed, which included the old C2, several previously unclassified sequences and previously designated C14. In particular, we identified a novel subgenotype, tentative C14, which was well supported by phylogenetic analysis and sequence divergence of >4%.Conclusions/SignificanceA number of misclassifications in the subgenotyping of genotype C HBV have been identified in this study. After correcting the misclassifications, we proposed a better classification for the subgenotyping of genotype C HBV, in which a novel quasi-subgenotype C2 and a novel subgenotype, tentative C14, were described. Based on this large-scale analysis, we propose that a novel subgenotype should only be reported after a complete comparison of all relevant sequences rather than a few representative sequences only.
Highlights
Ten genotypes [1,2,3] and more than 30 subgenotypes [4] of Hepatitis B virus (HBV) have been identified based on the general rule that different genotypes should diverge by at least 8% [5] and different subgenotypes should diverge by at least 4% over the entire genome [6]
We proposed a better classification for the subgenotyping of genotype C HBV, in which a novel quasi-subgenotype C2 and a novel subgenotype, tentative C14, were described
Subgenotype C6 was first proposed by analyzing the S gene sequences and preC-C gene sequences from Papua, Indonesia [13], which was later confirmed by complete genome sequences in 2009 [14]
Summary
Ten genotypes (from genotype A to J) [1,2,3] and more than 30 subgenotypes [4] of HBV have been identified based on the general rule that different genotypes should diverge by at least 8% [5] and different subgenotypes should diverge by at least 4% over the entire genome [6]. To avoid potential confusion in the delimitation of subgenotypes, Mulyanto and colleagues renamed their C7 as C8 in 2010 [18] They proposed a novel subgenotype C9, which they originally reported as an unclassifiable subgenotype [18]. Subgenotype C10 was isolated from Indonesia where a few novel subgenotypes, such as B7, B8 and C7 to C9, were identified [18]. Mulyanto et al further described four novel subgenotypes C13 to C16 [21] These four subgenotypes were isolated from Papua, Indonesia. More than ten subgenotypes of genotype C Hepatitis B virus (HBV) have been reported, including C1 to C16 and two C/D recombinant subgenotypes (CD1 and CD2), inconsistent designations of these subgenotypes still exist
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