Limited Effects of Fasting on Hepatitis B Virus (HBV) Biosynthesis in HBV Transgenic Mice

Nuclear receptors have a unique role in governing hepatitis B virus (HBV) transcription and replication. Hepatocyte nuclear factor 4 alpha (HNF4 alpha) and retinoid X receptor alpha (RXR alpha) plus peroxisome proliferator-activated receptor alpha (PPAR alpha) have been shown to support viral biosynthesis in nonhepatoma cells in the absence of additional liver-enriched transcription factors. However, the in vivo importance of these nuclear receptors in HBV biosynthesis has been investigated only to a limited extent. Fasting has been shown to activate gluconeogenesis, in part, by activating PPAR gamma coactivator 1 alpha, which in turn leads to activation of HNF4 alpha- and RXR alpha/PPAR alpha-mediated transcription. As HBV pregenomic RNA synthesis is primarily believed to be regulated by HNF4 alpha under normal physiological conditions, it was of interest to determine the effect of fasting on the levels of HBV RNA and DNA synthesis. Fasting was shown to rather modestly increase the levels of viral proteins, transcripts, and replication intermediates in the HBV transgenic mouse model of chronic viral infection, suggesting that caloric restriction may modulate viremia to some extent during natural infection.