Starved for Infection

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Science  27 Oct 2006:
Vol. 314, Issue 5799, pp. 567
DOI: 10.1126/science.314.5799.567b

About 600,000 people die each year from hepatitis B virus (HBV)-related liver disease or hepatocellular carcinoma. Recent vaccination programs have been highly effective in preventing new HBV infections, but millions of chronically infected individuals require treatment. Successful therapy development depends in part on identifying host factors in the liver essential for the HBV life cycle.

Working with an HBV-luciferase construct in mice to track viral gene expression in real time, Shlomai et al. found that HBV transcription is tightly coupled to the nutritional state of the animals. Short-term starvation of the mice caused a robust induction of HBV expression that was completely reversible by re-feeding. This effect was dependent on peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a transcriptional regulatory protein that activates host metabolic genes expressed in response to starvation, including those involved in liver gluconeogenesis. The shared regulation of HBV genes and host metabolic genes suggests that the fluctuating nature of HBV infection may be due not only to mutational changes in the virus but also to changes in the host's nutritional state, a hypothesis offering new possibilities for therapy. — PAK

Proc. Natl. Acad. Sci. U.S.A. 103, 16003 (2006)

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