Abstract
BackgroundCpG islands in hepatitis B virus (HBV) genome are potential targets for methylation mediated gene silencing, and may be involved in the pathogenesis of HBV infection. To date, their characteristics in HBV quasispecies (QS) remain largely unknown. The purpose of this study was to investigate the characteristics of CpG islands in HBV QS. MethodsForty patients diagnosed as acute hepatitis B (AHB, n = 10), immune-tolerant HBV carriers (IT, n = 9), chronic hepatitis B (CHB, n = 11), or acute on chronic liver failure (ACLF, n = 10), were enrolled in this case–control study. A total of 599 clones were isolated, and full-length HBV genomes were sequenced.ResultsCpG island II (CGII) in AHB group was shorter in length and its QS heterogeneity was lower than that in the chronic infection group. Among the chronic infection subgroups, CGII and CpG island III (CGIII) in IT group were longer and their heterogeneity was lower compared to CHB and ACLF groups. Length of CGII correlated with HBV DNA levels positively while the complexity and diversity of CGII correlated with HBV DNA levels negatively. Moreover, CGII and CGIII were shorter in genotype B than those in genotype C, while QS complexity and diversity of either CGII or CGIII had no significant difference between genotype B and C.ConclusionsOverall, our results suggest that the distribution, length and QS heterogeneity of CpG islands in full-length HBV genome differ across clinical phases of infection, of which the mechanism warrants further study.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-3192-3) contains supplementary material, which is available to authorized users.
Highlights
CpG islands in hepatitis B virus (HBV) genome are potential targets for methylation mediated gene silencing, and may be involved in the pathogenesis of HBV infection
Among 40 patients, patients were diagnosed as acute hepatitis B (AHB), 9 patients in high replicative, low inflammatory phase (Gish et al 2015), patients with chronic hepatitis B (CHB), and the other 10 with acute on chronic liver failure (ACLF)
Distribution of CpG islands in patients with different phases of infection Experiments of molecular cloning and sequencing were performed in our previous study (Yang et al 2015), and the characteristics of CpG islands in full-length HBV genomes of 599 clones were analyzed and new data were generated in the present study (Genbank submission numbers: KU963799–KU964397)
Summary
CpG islands in hepatitis B virus (HBV) genome are potential targets for methylation mediated gene silencing, and may be involved in the pathogenesis of HBV infection. To date, their characteristics in HBV quasispecies (QS) remain largely unknown. CpG islands which are CpG-rich regions in HBV genome, are potential targets for methylation mediated gene silencing and are related with virus replication (Vivekanandan et al 2010). There is no datum from reallife study to explore the characteristics of CpG islands in HBV genome from different phases of infection
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