Hepatitis B virus pathogenesis and APOBEC3 cytidine deaminases

Abstract

APOBEC3 editing enzymes inhibit retroviruses by cytidine deamination in minus-strand cDNA, leading to G to A hypermutated proviruses, and by less well characterized inhibition of retroviral replication independently of catalysis. The cytidine deaminases A3B, A3C, A3F and A3G deaminate cytidine residues in HBV minns-strand cDNA,resulting in G to A hypermutated genomes in the serum of HBV infection patients. A3B, A3F and A3G directly inhibit HBV reverse transcription independently of deaminase activity. In human liver, A3B, A3F and A3G are expressed to low levels and stimulated with interferon A3G is induced to levels sufficient for HBV inhibition. A3B and A3G preferentially mutate the HBV X gene leading to the truncated HBV X variants in HBV associated liver cancer. APOBEC3 cytidine deaminases likely play a role in noncytolytiC clearance of HBV in vivo. In the article, some relations between APOBEC3 and HBV inhibition are reviewed. Key words: Hepatitis B virus; APOBEC3; Pathogenesis; Immunity