Relationship of serological subtype, basic core promoter and precore mutations to genotypes/subgenotypes of hepatitis B virus

Abstract

Using phylogenetic analysis and pairwise comparison of 670 complete hepatitis B virus (HBV) genomes, we demonstrated that nucleotide divergence greater than 7.5% can be used to separate strains into genotypes A–H. Strains can be separated into subgenotypes when two criteria are met: nucleotide divergence of about 4% but less than 7.5% and good bootstrap support. There is a highly statistically significant association between serological subtypes and genotypes (χ2‐test for association, P < 0.0001): adw is associated with genotypes A, B, F, G, and H, adr with C and ayw with D and E. The logistic regression method showed that 1802–1803CG are characteristic of genotypes A, D, and E whereas 1802–1803TT are characteristic of genotypes B, C, and F. 1858C is positively associated with genotypes A, F, and H and 1858T with genotypes B, D, and E. Subgenotypes C2, F1/F4 can be differentiated from subgenotypes C1, F2/F3, respectively, because the latter have 1858C as opposed to 1858T in the former. 1888A was positively associated with subgenotype A1 and TAA at 1817 with genotype G. The Haploplot method revealed high linkage between loci 1858 and 1896 but strong evidence of recombination between loci 1862 and 1896. Loci 1809–1812, 1862, and 1888 may have co‐evolved. Using a computer program, we showed that serological subtype deduced from the S region (position 155–835) and mutations/variations within the basic core promoter/precore region (1653–1900), allowed genotyping of HBV with 97% sensitivity and 99% specificity. Certain subgenotypes or subgenotype groups could also be differentiated. J. Med. Virol. 80:27–46, 2008. © 2007 Wiley‐Liss, Inc.

Hepatitis B Virus Genome Analysis in Patients of Hepatocellular Carcinoma and Asymptomatic Carriers from Northern, Southern and North East India

“…Several molecular methods have been used for HBV genotyping like nucleotide sequencing in pre-S/S regions; but full-length genome sequencing remains the best method. Although the common genotyping method uses the surface gene amplification process, there is an exception as HBV strains can be accurately genotyped by sequencing two regions of the HBV genome as well, namely the S region and BCP/PC region 62 .…”

Hepatitis B Virus Genetic Diversity: Disease Pathogenesis

“…Galibert et al [51], published the first sequence of a complete HBV genome. Later, Okamoto et al [52], analyzed 18 full length genomes and divided them into four groups or genotypes, named as A to D. The ability of HBV to adapt to the host genetics as well as immunogenic environment by genetic variation, led to the evolution of eight established genotypes (A-H): [8,53] and two putative genotypes (I and J), each corresponding to a rather well-defined geographical distribution (Table 1). HBV genotypes A and D have worldwide distribution, whereas genotypes B and C are mostly found in Asia.…”

Hepatitis B Virus (HBV) Variants in Hemodialysis Patients

“…Recently, two novel genotypes, I and J, the former described in Laos and Vietnam (Olinger et al, 2008;Tran et al, 2008), and the latter in Japan (Tatematsu et al, 2009), have been proposed, but their designation as new genotypes is still controversial. There is a great deal of diversity within the genotypes and this has led to the division of some genotypes into different subgenotypes, such as A1-A6 in HBV of genotype A (HBV/A), B1-B8 in HBV/B, C1-C10 in HBV/C, D1-D7 in HBV/D, and F1-F4 in HBV/F (Huy et al, 2006;Kramvis et al, 2008;Lusida et al, 2008;Meldal et al, 2009;Mulyanto et al, 2009;Norder et al, 2004;Nurainy et al, 2008;Pourkarim et al, 2010;Sakamoto et al, 2006;Utsumi et al, 2009;Wang et al, 2007). …”