Abstract
DNA methylation is being increasingly recognized to play a role in regulation of hepatitis B virus (HBV) gene expression. The aim of this study was to compare the CpG island distribution among different HBV genotypes. We analyzed 176 full-length HBV genomic sequences obtained from the GenBank database, belonging to genotypes A through J, to identify the CpG islands in the HBV genomes. Our results showed that while 79 out of 176 sequences contained three conventional CpG islands (I–III) as previously described, 83 HBV sequences harbored only two of the three known islands. Novel CpG islands were identified in the remaining 14 HBV isolates and named as CpG island IV, V, and VI. Among the eight known HBV genotypes and two putative genotypes, while HBV genomes containing three CpG islands were predominant in genotypes A, B, D, E, and I; genotypes C, F, G, and H tended to contain only two CpG islands (II and III). In conclusion, the CpG islands, which are potential targets for DNA methylation mediated by the host functions, differ among HBV genotypes, and these genotype-specific differences in CpG island distribution could provide new insights into the understanding of epigenetic regulation of HBV gene expression and hepatitis B disease outcome.
Highlights
Hepatitis B virus (HBV) causes chronic infections in more than 350 million people worldwide, resulting in liver diseases ranging from chronic hepatitis to hepatocellular carcinoma (HCC) [1]
Genomes, we mapped the islands in representative sequences of the ten HBV genotypes (Figure 1), using MethPrimer and CpG Plot to identify the location and size of CpG islands I, II, and III within each sequence
Both programs were in agreement for all CpG islands in all sequences analyzed in the study
Summary
Hepatitis B virus (HBV) causes chronic infections in more than 350 million people worldwide, resulting in liver diseases ranging from chronic hepatitis to hepatocellular carcinoma (HCC) [1]. Ten HBV genotypes (A–J) have been classified [3,4,5] based on an intergroup divergence of 8% or more in the complete genomic sequences, with genotype I and J still speculative. Genotypes A and D have a wide global distribution [6,7,8,9,10,11], while genotypes B and C are highly prevalent in Asia [12,13,14,15]. The two newly identified and putative genotypes, I and J, are found in East and Southeast Asia [22,23] and Japan, respectively
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