Fatal exacerbation of type B chronic hepatitis triggered by changes in relaxed circular viral DNA synthesis and virion secretion.
Virological features of fulminant liver disease-causing hepatitis B virus (HBV) have not been fully elucidated. We studied longitudinally the viruses obtained before and after fulminant liver disease in a patient with chronic HBV infection showing fatal exacerbation. HBV strains were obtained before and after exacerbation (designated as FEP1 and FEP2). Their virological features were investigated by in vitro transfection. FEP1 and FEP2 possessed higher activity of overall HBV DNA synthesis than the wild-type. FEP1 lacked competence for relaxed circular (RC) HBV DNA synthesis and RC HBV DNA-containing virion secretion, but FEP2 maintained it. Chimeric analysis revealed that the preS/S gene, where FEP1 had a considerable number of mutations and deletions but FEP2 did not, was responsible for impaired RC HBV DNA synthesis and virion secretion. Furthermore, incompetence of FEP1 strain was transcomplemented by the preS/S protein of wild-type strain. In conclusion, the viral strain after exacerbation showed resurgent RC HBV DNA synthesis and virion secretion, which was caused by conversion of the preS/S gene from a hypermutated to hypomutated state. This may have been responsible for disease deterioration in the patient. This is a novel type of HBV genomic variation associated with the development of fulminant liver disease.
Ohkawa
Kazuyoshi
K
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita 565-0871, Japan.
Takehara
Tetsuo
T
Ishida
Hisashi
H
Kodama
Takahiro
T
Shimizu
Satoshi
S
Hikita
Hayato
H
Yamamoto
Masashi
M
Kohga
Keisuke
K
Sasakawa
Akira
A
Uemura
Akio
A
Sakamori
Ryotaro
R
Yamaguchi
Shinjiro
S
Li
Wei
W
Hosui
Atsushi
A
Miyagi
Takuya
T
Tatsumi
Tomohide
T
Katayama
Kazuhiro
K
Hayashi
Norio
N
D000369:Aged, 80 and over; D004261:DNA Replication; D004270:DNA, Circular / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics*; D014644:Genetic Variation; D006514:Hepatitis B Surface Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000821:virology*; D006801:Humans; D017114:Liver Failure, Acute / Q000821:virology*; D008297:Male; D011498:Protein Precursors / Q000235:genetics; D014771:Virion / Q000235:genetics / Q000502:physiology; D057074:Virus Release / Q000235:genetics / Q000502:physiology
D004270:DNA, Circular; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; C050807:presurface protein 2, hepatitis B surface antigen