Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.antiviral.2013.11.012
Title: Inhibition of human cytomegalovirus replication by overexpression of CREB1
Authors: Chia, Y.L.
Ng, C.H.
Lashmit, P.
Chu, K.L.
Lew, Q.J.
Ho, J.P.
Lim, H.L.
Nissom, P.M.
Stinski, M.F.
Chao, S.-H. 
Keywords: CREB1
Human cytomegalovirus
Major immediate-early genes
NF-κB
SP1
SP3
Issue Date: Feb-2014
Citation: Chia, Y.L., Ng, C.H., Lashmit, P., Chu, K.L., Lew, Q.J., Ho, J.P., Lim, H.L., Nissom, P.M., Stinski, M.F., Chao, S.-H. (2014-02). Inhibition of human cytomegalovirus replication by overexpression of CREB1. Antiviral Research 102 (1) : 11-22. ScholarBank@NUS Repository. https://doi.org/10.1016/j.antiviral.2013.11.012
Abstract: Expression of the human cytomegalovirus (HCMV) major immediate-early (MIE) genes is regulated by a strong enhancer-containing promoter with multiple binding sites for various transcription factors, including cyclic AMP response element binding protein 1 (CREB1). Here we show that overexpression of CREB1 potently blocked MIE transcription and HCMV replication. Surprisingly, CREB1 still exhibited strong inhibition of the MIE promoter when all five CREB binding sites within the enhancer were mutated, suggesting that CREB1 regulated the MIE gene expression indirectly. Promoter deletion analysis and site-directed mutagenesis identified the region between -130 and -50 upstream of the transcription start site of the MIE gene as the "CREB1 responsive region". Mutations of SP1/3 and NF-κB binding sites within this region interrupted the inhibitory effect induced by CREB1 overexpression. Our findings suggest that overexpression of CREB1 can cause repression of HCMV replication and may contribute to the development of new anti-HCMV strategies. © 2013 Elsevier B.V. All rights reserved.
Source Title: Antiviral Research
URI: http://scholarbank.nus.edu.sg/handle/10635/126733
ISSN: 01663542
DOI: 10.1016/j.antiviral.2013.11.012
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