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Published online ahead of print on 4 March 2009 as doi:10.1099/vir.0.006007-0
Journal of General Virology 2009;90:1246.

A more recent version of this article appeared on May 1, 2009 J Gen Virol (2009), DOI 10.1099/vir.0.006007-0
© 2009 Society for General Microbiology
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Prospero-related homeobox protein (Prox1) inhibits hepatitis B virus replication through repressing multiple cis regulatory elements

Jun Qin1, Jianwei Zhai1, Ran Hong1, Shifang Shan1, Yuying Kong1, Yumei Wen2, Yuan Wang1, Jing Liu2 and Youhua Xie3,4

1 SLMB, Institute of Biochemistry and Cell Biology, SIBS, CAS;
2 Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University;
3 Shanghai Medical College, Fudan University

4 E-mail: yhxie{at}sibs.ac.cn

Hepatitis B virus (HBV) gene transcription is controlled by viral promoters and enhancers whose activities are regulated by a number of cellular factors as well as viral encoded proteins. Negative regulation of HBV cis-element activities by cellular factors has been less widely reported compared to their activation. In this study, we report that nuclear factor Prospero-related homeobox protein (Prox1) represses HBV antigen expression and genome replication in cultured hepatocytes. By using reporter gene analysis, three of the four HBV promoters, namely the enhancer II/core promoter (ENII/Cp), preS1 promoter (Sp1) and enhancer I/X promoter (ENI/Xp) were identified as targets for Prox1-mediated repression. Mechanistic analysis then revealed that for ENII/Cp, Prox1 serves as a corepressor of liver receptor homologue 1 (LRH-1) and down-regulates LRH-1-mediated activation of ENII/Cp, whereas for Sp1, Prox1 represses Sp1 activity partially through directly interacting with hepatocyte nuclear factor 1 (HNF-1). Identification of Prox1 as an HBV repressor will help in the understanding of detailed interactions between viral cis-elements and host cellular factors and may also form the basis for new anti-HBV intervention therapeutics.

Received 30 July 2008; accepted 23 January 2009.




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