Foxa deficiency restricts hepatitis B virus biosynthesis through epigenic silencing.

Unlabelled: In the hepatis B virus (HBV) transgenic mouse model of chronic infection, the forkhead box protein A/hepatocyte nuclear factor 3 (Foxa/HNF3) family of pioneer transcription factors are required to support postnatal viral demethylation and subsequent HBV transcription and replication. Liver-specific Foxa-deficient mice with hepatic expression of only Foxa3 do not support HBV replication but display biliary epithelial hyperplasia with bridging fibrosis. However, liver-specific Foxa-deficient mice with hepatic expression of only Foxa1 or Foxa2 also successfully restrict viral transcription and replication but display only minimal alterations in liver physiology.

Ten-eleven translocation (Tet) methylcytosine dioxygenase-dependent viral DNA demethylation mediates hepatitis B virus (HBV) biosynthesis.

Liver-specific ten-eleven translocation (Tet) 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 is only observed in a very limited number of pericentral hepatocytes in a pattern that is similar to glutamate-ammonia ligase (Glul), a β-catenin target gene.

Distinct phenotypic spectra of hepatocellular carcinoma in liver-specific tumor suppressor-deficient hepatitis B virus transgenic mice.

The hepatitis B virus (HBV) transgenic mouse model was used to interrogate the origins of HCC heterogeneity. HBV biosynthesis was used as a marker of liver tumor heterogeneity. Principal component and correlation analysis of HBV and cellular transcript levels demonstrated major differences within and between the gene expression profiles of Apc-deficient, Apc-deficient Pten-deficient, and Pten-deficient HCC.

Disassembly of the TRIM23-TBK1 Complex by the Us11 Protein of Herpes Simplex Virus 1 Impairs Autophagy.

The Us11 protein encoded by herpes simplex virus 1 (HSV-1) functions to impair autophagy; however, the molecular mechanisms of this inhibition remain to be fully established. Here, we report that the Us11 protein targets protein 23 (TRIM23), which is a key regulator of autophagy-mediated antiviral defense mediated by TANK-binding kinase 1 (TBK1). In virus-infected cells, the Us11 protein drastically reduces the formation of autophagosomes mediated by TRIM23 or TBK1.