Hepatitis B Virus of Genotype B with or without Recombination with Genotype C over the Precore Region plus the Core Gene

Abstract

The entire nucleotide sequences of 70 hepatitis B virus (HBV) isolates of genotype B (HBV/B), including 38 newly determined and 32 retrieved from the international DNA database (DDBJ/EMBL/GenBank), were compared phylogenetically. Two subgroups of HBV/B were identified based on sequence divergence in the precore region plus the core gene, one with the recombination with genotype C and the other without it. The analysis over the entire genome of HBV/B by the SimPlot program located the recombination with genotype C in the precore region plus the core gene spanning nucleotide positions from 1740 to 1838 to 2443 to 2485. Within this genomic area, HBV/B strains with the recombination had higher nucleotide and amino acid homology to genotype C than those without the recombination (96.9 versus 91.1% in nucleotides and 97.0 versus 92.9% in amino acids). There were 29 HBV/B strains without the recombination, and they were all recovered from carriers in Japan. The remaining 41 HBV/B isolates having the recombination with genotype C were from carriers in China (12 strains), Hong Kong (3 strains), Indonesia (4 strains), Japan (3 strains), Taiwan (4 strains), Thailand (3 strains), and Vietnam (12 strains). Due to the frequency of the distribution of HBV/B without the recombination (29 of 32 isolates, or 91%) and the fact that it was exclusive to Japan, it was provisionally classified into the Bj (j standing for Japan) subgroup, and HBV/B with the recombination was classified into the Ba (a for Asia) subgroup. Virological differences between HBV/Bj and HBV/Ba may be reflected in the severity of clinical disease in the patients infected with HBV of genotype B, which seems to be under strong geographic influences in Asia.

Analysis of the entire nucleotide sequence of hepatitis B virus genotype B in the Philippines reveals a new subgenotype of genotype B

“…Similar to the study reported by Sugauchi et al (2002), a comparison of nucleotide similarities from positions 1814 to 2452 in the precore and core gene of the present five isolates from the Philippines and representative HBV/B isolates from the other four subgenotypes, B1-B4, with isolates from HBV/C and B1 is shown in Supplementary Table S1 in JGV Online. The divergences confirmed that HBV/B in the Philippines had recombined with HBV/C in the precore and core gene, like in B2, B3 and B4.…”

“…Ba (B2, B3 and B4) has recombined with genotype C and has a higher prevalence of HBe antigen, so it manifests a more severe clinical course than Bj (B1) (Sugauchi et al, 2002). Thus, HBV needs to be examined with regards not only to its genotype, but also to its subgenotypes.…”

“…We compared the precore and core sequences of our five clones from the Philippines and four previous isolates from subgenotypes B1-B4 with HBV/C and HBV/B1 by following the method of Sugauchi et al (2002Sugauchi et al ( , 2003. The GenBank accession numbers and the countries from which they were derived are as follows: HBV/C, AB014378 (Japan) and D23684 (Japan); HBV/B1, AB073845 (Japan) and AB073855 (Japan).…”

Influence of hepatitis B virus genotypes on the progression of chronic type B liver disease

“…This fact suggests different virologic, host, and environmental factors in patients with genotype B between Japan and Taiwan. Recently, Sugauchi et al 24 reported that there were virologic differences between HBV genotype B strains from Japanese and those from other Asian patients, including Taiwanese. 24 This may be a clue to explaining the inconsistent findings in HCC patients between Japan and Taiwan.…”

Role of viral factors in the natural course and therapy of chronic hepatitis B

“…HBV subgenotype A1 appears to be associated with low serum HBV DNA levels as well as a low prevalence of serum HBeAg and is implicated in the high incidence of HBV-related HCC in Africa [61]; whereas subgenotype A2 has a higher rate of sustained remission after HBeAg seroconversion and a lower rate of liver-related death than other genotypes during long-term follow-up [62,63]. Sugauchi et al found that positivity of HBeAg is significantly more frequent in carriers of subgenotype B1 than B2 [64]. An additional study analyzed the distribution of HBV subgenotypes in 296 HBV-related HCC patients collected from all over Japan [65].…”