Characterization of Full-Length Genomes of Hepatitis B Virus Quasispecies in Sera of Patients at Different Phases of Infection.
Hepatitis B virus (HBV) infection results in different clinical presentation due to different levels of immune response. Our study aimed to characterize HBV full-length genome quasispecies (QS) in patients with different phases of infection to better understand its pathogenesis. Forty treatment-naive HBV-infected patients were enrolled, including 10 cases of acute hepatitis B (AHB), 9 cases of immunotolerant (IT) HBV carriers, 11 cases of chronic hepatitis B (CHB), and 10 cases of acute-on-chronic liver failure (ACLF). The present study was conducted by clone-based sequencing. QS heterogeneity within each open reading frame was calculated. The mutation frequency index (MFI) and amino acid variations within the large HBsAg, HBcAg, and HBxAg regions were analyzed based on the different infection phases. In total, 606 HBV full-length sequences were obtained. HBV QS had higher heterogeneity in ACLF and CHB than that in IT among chronically infected individuals. AHB patients had the lower QS heterogeneity at onset than those with chronic infection. ACLF patients had the highest frequency of mutations in the core promoter and precore region. A triple mutation (A1762T/G1764A/G1896A) was observed more frequently in genotype C than in genotype B. The MFI indicated that specific peptides of the studied regions had more frequent mutations in ACLF. Furthermore, several amino acid variations, known as T- and B-cell epitopes, were potentially associated with the immunoactive phase of infection. More HBV genome mutations and deletions were observed in patients with more severe diseases, particularly in specific regions of the core and preS regions, the clinical significance and mechanism of which need to be further investigated.
Emergency Department, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
Zhi-Tao
ZT
Yang
Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
Su-Yuan
SY
Huang
Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
Li
L
Chen
Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
Feng
F
Liu
Shanghai Center for Bioinformation Technology, Shanghai, China.
Xiao-Hui
XH
Cai
Shanghai Center for Bioinformation Technology, Shanghai, China.
Yang-Fan
YF
Guo
Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
Ming-Jie
MJ
Wang
Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
Yue
Y
Han
Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
De-Min
DM
Yu
Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
Jie-Hong
JH
Jiang
Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
Dong-Hua
DH
Zhang
Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
Qi-Ming
QM
Gong
Shanghai Center for Bioinformation Technology, Shanghai, China.
Guo-Qing
GQ
Zhang
Department of Infectious Diseases, The Sixth People's Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
Guo-Qing
GQ
Zang
Department of Hepatology, The Fifth People's Hospital, Wuxi, China.
Zhong-Hua
ZH
Lu
Department of Hepatology, The Fifth People's Hospital, Wuxi, China huanglihua1964@sina.com zhangxinxinrj@163.com.
Li-Hua
LH
Huang
Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China Translational Medicine Research Centre, Ruijin Hospital North, Shanghai Jiaotong University, School of Medicine, Shanghai, China huanglihua1964@sina.com zhangxinxinrj@163.com.
Xin-Xin
XX
Zhang
D000939:Epitopes / Q000235:genetics; D014644:Genetic Variation; D016679:Genome, Viral; D005838:Genotype; D006509:Hepatitis B / Q000473:pathology / Q000821:virology*; D006511:Hepatitis B Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D059645:Mutation Rate; D020125:Mutation, Missense; D017384:Sequence Deletion
D000939:Epitopes; D006511:Hepatitis B Antigens