Massive APOBEC3 Editing of Hepatitis B Viral DNA in Cirrhosis

摘要: DNA viruses, retroviruses and hepadnaviruses, such as hepatitis B virus (HBV), are vulnerable to genetic editing of single stranded by host cell APOBEC3 (A3) cytidine deaminases. At least three A3 genes up regulated interferon-α in human hepatocytes while ectopic expression activation induced deaminase (AICDA), an paralog, has been noted a variety chronic inflammatory syndromes including C infection. Yet virtually all studies HBV have confined themselves analyses virions from culture supernatants or serum where the frequency edited genomes is generally low (≤10−2). We decided look at nature cirrhotic samples taken during removal primary hepatocellular carcinoma. Forty-one tissue (10 alcoholic, 10 HBV+, 11 HBV+HCV+ HCV+) well 4 normal livers were studied. Compared liver, 5/7 significantly order: HCV±HBV>HBV>alcoholic cirrhosis. A3C A3D for groups interferon inducible A3G was over expressed associated cirrhosis, AICDA ∼50% these HBV/HCV samples. While can indeed edit ex vivo, dominant vivo with 35% being edited. Despite highly deleterious mutant spectra, small fraction survive contribute loss HBeAg antigenemia possibly HBsAg immune escape. In conclusion, cytokine storm responses HCV clearly regulates number major restriction factor HBV. Although spectrum resulting deleterious, very part, notably lightly genomes, might help evolve even escape responses.