Research ArticleHost-Pathogen Interactions

Inhibition of PP1 Phosphatase Activity by HBx: A Mechanism for the Activation of Hepatitis B Virus Transcription

Science Signaling  03 Jan 2012:
Vol. 5, Issue 205, pp. ra1
DOI: 10.1126/scisignal.2001906

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Inhibiting Dephosphorylation for Viral DNA Transcription

The transcription factor CREB [cyclic adenosine monophosphate (cAMP) response element–binding protein] is phosphorylated and activated downstream of cAMP production, whereas it is dephosphorylated and inactivated by protein phosphatase 1 (PP1). Cougot et al. previously showed that HBx, a protein produced by hepatitis B virus (HBV), increases the transcription of CREB target genes. Here, the authors show that HBV co-opts CREB in the transcription of its own DNA. Phosphorylation of CREB (and thus activity) recruited on HBV DNA was prolonged, an effect that was mediated by inhibition of PP1 activity by HBx. Because persistent liver infection with HBV is a risk factor for developing hepatocellular carcinoma, these results suggest that targeting HBx could be a way to attenuate HBV infection and reduce the risk of viral-induced cancer.