Limited effects of bile acids and small heterodimer partner on hepatitis B virus biosynthesis in vivo. J Virol 2012 Mar;86(5):2760-8
Date
12/16/2011Pubmed ID
22171277Pubmed Central ID
PMC3302260DOI
10.1128/JVI.06742-11Scopus ID
2-s2.0-84857806196 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
Multiple nuclear receptors, including hepatocyte nuclear factor 4α (HNF4α), retinoid X receptor α (RXRα) plus peroxisome proliferator-activated receptor α (PPARα), RXRα plus farnesoid X receptor α (FXRα), liver receptor homolog 1 (LRH1), and estrogen-related receptors (ERRs), have been shown to support efficient viral biosynthesis in nonhepatoma cells in the absence of additional liver-enriched transcription factors. Although HNF4α has been shown to be critical for the developmental expression of hepatitis B virus (HBV) biosynthesis in the liver, the relative importance of the various nuclear receptors capable of supporting viral transcription and replication in the adult in vivo has not been clearly established. To investigate the role of the nuclear receptor FXR and the corepressor small heterodimer partner (SHP) in viral biosynthesis in vivo, SHP-expressing and SHP-null HBV transgenic mice were fed a bile acid-supplemented diet. The increased FXR activity and SHP expression levels resulting from bile acid treatment did not greatly modulate HBV RNA and DNA synthesis. Therefore, FXR and SHP appear to play a limited role in modulating HBV biosynthesis, suggesting that alternative nuclear receptors are more critical determinants of viral transcription in the HBV transgenic mouse model of chronic viral infection. These observations suggest that hepatic bile acid levels or therapeutic agents targeting FXR may not greatly modulate viremia during natural infection.
Author List
Reese VC, Moore DD, McLachlan AAuthor
Vanessa Mcfadden MD Associate Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBile Acids and Salts
Cell Line
Dimerization
Female
Hepatitis B
Hepatitis B virus
Humans
Ligands
Liver
Male
Mice
Mice, Knockout
Mice, Transgenic
Protein Biosynthesis
Receptors, Cytoplasmic and Nuclear
Virus Replication
