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Journal of Virology, August 2008, p. 7313-7324, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.02581-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Transcription Factor YY1 and Its Associated Acetyltransferases CBP and p300 Interact with Hepatitis Delta Antigens and Modulate Hepatitis Delta Virus RNA Replication{triangledown}

Wen-Hung Huang,{dagger} Ru-Tsun Mai, and Yan-Hwa Wu Lee*

Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan, Republic of China

Received 4 December 2007/ Accepted 8 May 2008

Hepatitis delta virus (HDV) is a pathogenic RNA virus with a plant viroid-like genome structure. HDV encodes two isoforms of delta antigen (HDAg), the small and large forms of HDAg (SHDAg and LHDAg), which are essential for HDV RNA replication and virion assembly, respectively. Replication of HDV RNA depends on host cellular transcription machinery, and the exact molecular mechanism for HDV RNA replication is still unclear. In this study, we demonstrated that both isoforms of HDAg interact with transcription factor YY1 (Yin Yang 1) in vivo and in vitro. Their interaction domains were identified as the middle region encompassing the RNA binding domain of HDAg and the middle GA/GK-rich region and the C-terminal zinc-finger region of YY1. Results of sucrose gradient centrifugation analysis indicated the cosedimentation of the majority of SHDAg and a portion of the LHDAg with YY1 and its associated acetyltransferases CBP (CREB-binding protein) and p300 as a large nuclear complex in vivo. Furthermore, exogenous expression of YY1 or CBP/p300 in HDV RNA replication system showed an enhancement of HDV RNA replication. Interestingly, the acetyltransferase activity of p300 is important for this enhancement. Moreover, SHDAg could be acetylated in vivo, and treatment with cellular deacetylase inhibitor elevated the replication of HDV RNA and acetylation of SHDAg. All together, our results reveal that HDAg interacts with cellular transcription factor YY1 and its associated acetyltransferases CBP and p300 in a large nuclear complex, which in turn modulates the replication of HDV RNA.

* Corresponding author. Mailing address: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan 112, Republic of China. Phone: 886 2 2826 7124. Fax: 886 2 2826 4843. E-mail: yhwulee{at}ym.edu.tw

{triangledown} Published ahead of print on 14 May 2008.

{dagger} Present address: Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan 100, Republic of China.

Journal of Virology, August 2008, p. 7313-7324, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.02581-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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