G to A hypermutation of hepatitis B virus.
G to A hypermutation of the human immunodeficiency virus type 1 (HIV-1) is induced by a deaminase APOBEC3G and is related to host antiviral defense. APOBEC3G has also been found to reduce the replication of HIV-1 by an unknown mechanism. This enzyme also reduces the production of hepatitis B virus, although the mechanism for this action has not been clearly elucidated. The hypermutated hepatitis B virus (HBV) is rarely found in usual sequencing analyses. Using peptide nucleic acid mediated by polymerase chain reaction clamping, we detected the hypermutated HBV DNA in 1 of 8 patients with acute HBV infection and 4 of 10 with chronic HBV infection. In the latter group, hypermutated genomes were found only in eAb-positive patients. As much as 72.5% of G residues were mutated in the hypermutated clones. G to A substitutions were predominant in almost all clones sequenced compared with other substitutions. G to A mutated viral genomes also were found in HepG2-derived cell lines that continuously produced HBV into the supernatant. Both alpha and gamma interferon reduced virus production in these cell lines, but they did not alter the frequency of the hypermutation. Transcripts of APOBEC3G, as well as some other deaminases, were found in these cell lines. In conclusion, our results show that part of the minus strand DNA of HBV is hypermutated both in vitro (HepG2 cell lines) and in vivo. The role and mechanism of hypermutation in reducing HBV replication should be further investigated to understand the anti-HBV defense system.
Noguchi
Chiemi
C
Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Ishino
Hiromi
H
Tsuge
Masataka
M
Fujimoto
Yoshifumi
Y
Imamura
Michio
M
Takahashi
Shoichi
S
Chayama
Kazuaki
K
D000071480:APOBEC-3G Deaminase; D000328:Adult; D001483:Base Sequence; D002460:Cell Line; D003564:Cytidine Deaminase; D016679:Genome, Viral; D006515:Hepatitis B virus / Q000235:genetics*; D006526:Hepatitis C / Q000821:virology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009700:Nucleoside Deaminases; D011506:Proteins / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins; D014779:Virus Replication
D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase