INTERACTIONS BETWEEN MITOCHONDRIA AND THE ENIGMATIC HEPATITIS B VIRUS X PROTEIN PROVIDE CLUES TO VIRAL EVOLUTION AND PRO-CARCINOGENICITY. (February 2015)

• Record Type: Journal Article
• Authors: Shaw, Tim; Peel, Andrew
• Is Part Of: Pathology. Volume 47(2015)Supplement 1
• Publication Date: 2015-02
• Subjects: Pathology -- Periodicals; 616.0705
• DOI: 10.1097/01.PAT.0000461573.43523.27
• Languages: English
• ISSNs: 0031-3025

Abstract

Abstract : Background: Hepatitis B viruses (HBVs) are evolutionarily ancient pararetroviruses that infect endotherms (birds and mammals). Chronic HBV infection significantly increases the risk of development of liver cancer in mammals but not birds. The HBV regulatory protein X (HBx), which is degenerate in avian HBVs, has been implicated in carcinogenesis. Establishment of chronic infection involves hijacking of mitochondrial functions to support viral replication. HBx interacts specifically with mitochondria. Mitochondria and respiratory systems of birds and mammals are fundamentally different. Hypothesis and aim: HBx may sustain otherwise dysfunctional mitochondria. We aimed to discover biologically plausible mechanisms that could support this hypothesis. Methods and results: Interrogation of public databases revealed that HBx and thymine DNA glycosylase (TDG) share common domain architecture. TDG is essential for DNA repair in all life forms. The RAD23 genes of some crop plants encode proteins with similar domain with similar architecture, consistent with the involvement of RAD23 in base excision repair. Glycosyltransferases of some domesticated ungulates and some prokaryotic proteins involved in replication initiation also contain similar domains. Conclusions: Ancestral HBx genes were probably acquired from plants. Ungulates and plant pararetroviruses may have been involved in HBx gene transfer. HBx may facilitate both mitochondrial and HBV genome repair.