|Public on Nov 29, 2023
|Ten-eleven translocation (Tet) methylcytosine dioxygenases dependent viral DNA demethylation mediates in vivo hepatitis B virus (HBV) biosynthesis
|Hepatitis B virus
|Methylation profiling by high throughput sequencing
|Liver-specific ten-eleven translocation methylcytosine dioxygenases 2 and 3 (Tet2 plus Tet3)-deficient hepatitis B virus (HBV) transgenic mice fail to support viral biosynthesis. The levels of viral transcription and replication intermediates are dramatically reduced. Hepatitis B core antigen (HBcAg) is only observed in a very limited number of pericentral hepatocytes in a pattern that is similar to glutamate-ammonia ligase (Glul), a -catenin target gene. HBV transcript abundance in Tet-deficient mice resembles that observed in wild-type neonatal mice. Furthermore, the RNA levels of several -catenin target genes including Glul, Lhpp, Notun, Oat, Slc1a2 and Tbx3, in Tet-deficient mice was also similar to that observed in wild-type neonatal mice. As HBV transcription is regulated by -catenin, these finding support the suggestion that neonatal Tet-deficiency might limit -catenin target gene expression, limiting viral biosynthesis. Additionally, HBV transgene DNA displays increased 5-methylcytosine (5mC) frequency at CpG sequences consistent with neonatal Tet-deficiency being responsible for decreased developmental viral DNA demethylation mediated by 5mC oxidation to 5-hydroxymethylcytosine (5hmC), a process that might be responsible for the reduction in cellular -catenin target gene expression and viral transcription and replication.
|Liver-specific Tet2-delete, Tet3-deleted and Tet2 plus Tet3-deleted HBV transgenic mice were generated and characterized to determine the role for Tet enzymes in the liver-specific demethylation of HBV transgene DNA which is associated with viral biosynthesis in this model of chronic infection.
|Matrenec R, Oropeza CE, Dekoven E, Tarnow G, Maienschein-Cline M, Chau CS, Green SJ, McLachlan A
|Sep 06, 2023
|Last update date
|Feb 28, 2024
|University of Illinois at Chicago
|Research Resources Center
|Center for Research Informatics
|1819 W Polk Ave, Rm 336 M/C 789
|Illumina MiSeq (Hepatitis B virus)