Evidence that methylation of hepatitis B virus covalently closed circular DNA in liver tissues of patients with chronic hepatitis B modulates HBV replication.
|
| Abstract |
Epigenetic factors may modulate chronic Hepatitis B viral infection by affecting virion gene transcription. The aim of this study was to compare the methylation status of the intrahepatic covalently closed circular DNA (cccDNA) CpG island 2 and HBV replication capability. HBV cccDNA was extracted from liver biopsies of 55 HBsAg-positive patients with chronic hepatitis B (32 HBeAg-positive and 23 HBeAg-negative), and was analyzed for methylation status and quantity. The two Hpa II recognition sequences CCpGG in the CpG island 2 were methylated in infected liver tissues from 24 (43.6%) of 55 patients. Positive ratios of cccDNA methylation were significantly higher in HBeAg-negative patients (15/23, 65.2%) than HBeAg-positive patients (9/32, 28.1%) (P < 0.05). The percentage of methylated-cccDNA/total-cccDNA of HBeAg-negative samples (a median of 48%, ranging from 5% to 83%) was significantly higher (P < 0.001) than HBeAg-positive samples (a median of 14%, ranging from 0.26% to 35%). Ratios of relaxed circular DNA (rcDNA) to cccDNA molecules revealed that cccDNA methylation correlated with impaired virion productivity in HBeAg-positive individuals (P < 0.05). The bisulfite DNA sequencing showed that methylation density was significantly higher in HBeAg-negative than in HBeAg-positive patients (P < 0.05). The methylation level of the CpG island 2 of the cccDNA in HBeAg-negative patients was higher than that in HBeAg-positive patients, suggesting that HBV cccDNA methylation may be relevant to replication capability of HBV.
|
|---|---|
| Authors | Yanhai Guo, Yongnian Li, Shijie Mu, Ju Zhang, Zhen Yan |
| Journal | Journal of medical virology (J Med Virol) Vol. 81 Issue 7 Pg. 1177-83 (Jul 2009) ISSN: 1096-9071 [Electronic] United States |
| PMID | 19475606 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright 2009 Wiley-Liss, Inc. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!