G-to-A Hypermutation in Hepatitis B Virus (HBV) and Clinical Course of Patients with Chronic HBV Infection

BackgroundThe apolipoprotein B messenger RNA editing enzyme, catalytic polypeptide–like family of cytidine deaminases induce G-to-A hypermutation in hepatitis B virus (HBV) genomes and play a role in innate antiviral immunity. The clinical relevance of this protein family is unknown MethodsWe analyz...

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Bibliographic Details
Published in:The Journal of infectious diseases 2009-06, Vol.199 (11), p.1599-1607
Main Authors: Noguchi, Chiemi, Imamura, Michio, Tsuge, Masataka, Hiraga, Nobuhiko, Mori, Nami, Miki, Daiki, Kimura, Takashi, Takahashi, Shoichi, Fujimoto, Yoshifumi, Ochi, Hidenori, Abe, Hiromi, Maekawa, Toshiro, Tateno, Chise, Yoshizato, Katsutoshi, Chayama, Kazuaki
Format: Article
Language:English
Subjects:
Adult
Aged
Animals
Antivirals
Biological and medical sciences
Cell Line, Tumor
DNA
Female
Fundamental and applied biological sciences. Psychology
Genome, Viral
Genomes
Hepatitis antigens
Hepatitis B - blood
Hepatitis B - genetics
Hepatitis B e Antigens - blood
Hepatitis B virus
Hepatitis B virus - genetics
Hepatocytes
HIV 1
HIV Infections - complications
Human viral diseases
Humans
Infections
Infectious diseases
Male
Medical sciences
Mice
Microbiology
Miscellaneous
Mutation
Oncogene Proteins, Fusion - genetics
Polymerase chain reaction
Polymorphism, Single Nucleotide
RNA, Messenger - genetics
RNA, Viral - genetics
T lymphocytes
Transfection
Viral diseases
Viral hepatitis
Virology
Viruses
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Summary:BackgroundThe apolipoprotein B messenger RNA editing enzyme, catalytic polypeptide–like family of cytidine deaminases induce G-to-A hypermutation in hepatitis B virus (HBV) genomes and play a role in innate antiviral immunity. The clinical relevance of this protein family is unknown MethodsWe analyzed 33 instances in which 17 patients with chronic HBV infection experienced >2 increases of >100 IU/L in alanine aminotransferase (ALT) level; we used a quantitative differential DNA denaturation polymerase chain reaction assay to quantify the hypermutated HBV genomes observed during 21 of these 33 increases in ALT level ResultsOf the 9 increases in ALT level that involved a >5-fold increase (relative to basal levels) in the number of hypermutated genomes observed, 8 were associated with a >2-log reduction in plasma HBV DNA level. In contrast, a corresponding decrease in plasma HBV DNA level was observed for only 1 of the 12 increases in ALT level that did not involve an increase in the number of hypermutated genomes (P
ISSN:0022-1899
1537-6613
DOI:10.1086/598951