Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Letter to the Editor Intervirology 2009;52:321–322 DOI: 10.1159/000237739 Clarification Required for the Definition of Hepatitis B Virus Subgenotypes C1 and C2 Sang Hoon Ahn a, b Lilly Yuen b Peter Revill b a Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; b Victorian Infectious Diseases Reference Laboratory, North Melbourne, Vic., Australia To the Editor Hepatitis B virus (HBV) has been classified into 8 major geno- types A to H, with an intergenotypic diversity of at least 8% in the full genome sequence. Genotypes A to D are the most common worldwide, with genotype A predominant in Western Europe, North America and Africa, genotypes B and C most frequent in Asia, and genotype D present in Mediterranean countries [1]. There is increasing evidence that HBV strains, even within the same genotype, differ in virological and clinical manifestation. Within the HBV genotypes, variability of between 4 and 7.5% has led to further classification into subgenotypes [1], although HBV subgenotypes are yet to be ratified by the International Commit- tee for the Taxonomy of Viruses (ICTV) [2]. The HBV genotype C is prevalent in Asia, where it causes more serious liver disease than genotype B [3]. In the 2004 report of Norder et al. [4], phylogenetic analysis of 66 complete genotype C genomes identified 4 groups of genotype C (C1–C4), with clear geographical clustering. The C1 subgenotype consisted of HBV strains from East Asia, including Japan, Korea and China, whilst the C2 subgenotype dominated in China, Thailand, Laos, Viet- nam and Bangladesh. The C3 subgenotype was confined to New Caledonia and Polynesia and subgenotype C4 was confined to Australian aborigines in Northeast Australia. Subsequently, a C5 subgenotype has also been identified in the Philippines [5]. Published online: September 17, 2009 Peter Revill, PhD Molecular Research and Development Victorian Infectious Diseases Reference Laboratory 10 Wreckyn St, North Melbourne, Vic. 3051 (Australia) Tel. +61 3 9342 2604, Fax +61 3 9342 2666, E-Mail peter.revill@mh.org.au © 2009 S. Karger AG, Basel 0300–5526/09/0526–0321$26.00/0 Accessible online at: www.karger.com/int AF223960 Malaysia 100 AB074755 Thailand 50 62 AF068756 Thailand 89 AB074756 Thailand 79 X14193 Korea D23684 Japan 100 AF182802 China 94 Y18857 China 50 X75656 Polynesia 99 AB048704 Australian Aborigines 61 AB241111 Philippines C1 Huy et al. Norder et al. C3 C4 C2 C2 C1 C5 Fig. 1. Phylogenetic relationships of representative genomic- length HBV genotype C nucleotide sequences, showing the dif- ferent classification system used by Norder et al. [4] and Huy et al. [6] for the same C1 and C2 sequences. The tree was generated us- ing the Neighbour Joining Program in Phylip (http://evolution. genetics.washington.edu/phylip.html). Bootstrap analysis was performed using 1,000 data sets and bootstrap values are present- ed at the nodes. Each sequence is designated by its accession num- ber and country of origin.