title: Characteristics of CpG Islands and their quasispecies of full-length hepatitis B virus genomes from patients at different phases of infection.
abstract: BACKGROUND
  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. The purpose of this study was to investigate the characteristics of CpG islands in HBV QS.
  
  
  METHODS
  Forty 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.
  
  
  RESULTS
  CpG 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.
  
  
  CONCLUSIONS
  Overall, 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.
authors.affiliation: Clinical Virology Research Laboratory, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025 China.|Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.|Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Rui Jin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Clinical Virology Research Laboratory, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025 China.|Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.|Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Rui Jin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Ming-Jie
authors.initials: MJ
authors.lastname: Wang
authors.affiliation: Clinical Virology Research Laboratory, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025 China.|Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.|Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Rui Jin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Su-Yuan
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Clinical Virology Research Laboratory, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025 China.|Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.|Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Rui Jin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Zhi-Tao
authors.initials: ZT
authors.lastname: Yang
authors.affiliation: Clinical Virology Research Laboratory, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025 China.|Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.|Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Rui Jin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: De-Min
authors.initials: DM
authors.lastname: Yu
authors.affiliation: Clinical Virology Research Laboratory, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025 China.|Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.|Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Rui Jin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Han
authors.affiliation: Clinical Virology Research Laboratory, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025 China.|Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.|Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Rui Jin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Zhu
authors.affiliation: Clinical Virology Research Laboratory, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025 China.|Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.|Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Rui Jin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Dao
authors.initials: D
authors.lastname: Huang
authors.affiliation: Clinical Virology Research Laboratory, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025 China.|Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.|Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Rui Jin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Qi-Ming
authors.initials: QM
authors.lastname: Gong
authors.affiliation: Clinical Virology Research Laboratory, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025 China.|Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.|Translational Medicine Research Center, Ruijin Hospital North, Shanghai Jiaotong University, School of Medicine, Shanghai, China.|Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Rui Jin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Zhang
keywords: CpG islands; Genetic heterogeneity; Genotype; Hepatitis B virus