TY - JOUR
T1 - Effect of viral DNA methylation on expression of hepatitis B virus proteins depends on the virus genotype
AU - Nakamura, Takuya
AU - Inoue, Jun
AU - Ninomiya, Masashi
AU - Kakazu, Eiji
AU - Iwata, Tomoaki
AU - Takai, Satoshi
AU - Sano, Akitoshi
AU - Kogure, Takayuki
AU - Shimosegawa, Tooru
AU - Masamune, Atsushi
N1 - Funding Information:
We thank Biomedical Research Unit of Tohoku University Hospital for technical support. This study was supported by Grants-in-Aid from Japan Society for the Promotion of Science (15K08981 and 19K08385) to JI.
Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - The frequency of HBV genomic methylation in the liver was reported to vary among patients, but the detailed mechanism is still unknown. In this study, the effects of HBV genome methylation on HBV replication were investigated in vitro. A total of 6 plasmids containing 1.24-fold the HBV genome of different genotypes (subgenotypes A1, A2, B1, and C2) were purified after in vitro methylation with CpG methyltransferase (M.SssI) and transfected into HepG2 cells. In genotype B and C strains, methylation markedly decreased the amount of hepatitis B e antigen (HBeAg) in the culture supernatant. A reduction of hepatitis B surface antigen (HBsAg) was found in some HBV strains but the reduction was smaller than that of HBeAg. There was no significant difference in particle-associated HBV DNA in the culture supernatant. These findings suggest that HBV genomic methylation might be involved in the HBeAg decline in genotype B and C, in part, and that the reduction of HBsAg was less than that of HBeAg. In conclusion, this study showed that the effect of HBV genomic methylation differs among HBV genotypes, suggesting a potential explanation for the different clinical outcomes of genotypes A, B, and C.
AB - The frequency of HBV genomic methylation in the liver was reported to vary among patients, but the detailed mechanism is still unknown. In this study, the effects of HBV genome methylation on HBV replication were investigated in vitro. A total of 6 plasmids containing 1.24-fold the HBV genome of different genotypes (subgenotypes A1, A2, B1, and C2) were purified after in vitro methylation with CpG methyltransferase (M.SssI) and transfected into HepG2 cells. In genotype B and C strains, methylation markedly decreased the amount of hepatitis B e antigen (HBeAg) in the culture supernatant. A reduction of hepatitis B surface antigen (HBsAg) was found in some HBV strains but the reduction was smaller than that of HBeAg. There was no significant difference in particle-associated HBV DNA in the culture supernatant. These findings suggest that HBV genomic methylation might be involved in the HBeAg decline in genotype B and C, in part, and that the reduction of HBsAg was less than that of HBeAg. In conclusion, this study showed that the effect of HBV genomic methylation differs among HBV genotypes, suggesting a potential explanation for the different clinical outcomes of genotypes A, B, and C.
KW - Genotype
KW - HBeAg
KW - HBsAg
KW - HBV
KW - Methylation
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U2 - 10.1007/s11262-020-01761-5
DO - 10.1007/s11262-020-01761-5
M3 - Article
C2 - 32361814
AN - SCOPUS:85084229951
SN - 0920-8569
VL - 56
SP - 439
EP - 447
JO - Virus Genes
JF - Virus Genes
IS - 4
ER -
