Inhibition of human cytomegalovirus replication by overexpression of CREB1

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• 作者：Yi Ling Chia ; Chew Har Ng ; Philip Lashmit ; Kai Ling Chu ; Qiao Jing Lew ; Jia Pei Ho ; Hsueh Lee Lim ; Peter Morin Nissom ; Mark F. Stinski ; Sheng-Hao Chao
• 关键词：Human cytomegalovirus ; Major immediate-early genes ; CREB1 ; NF-魏B ; SP1 ; SP3
• 刊名：Antiviral Research
• 出版年：February, 2014
• 年：2014
• 卷：102
• 期：Complete
• 页码：11-22
• 全文大小：1472 K

文摘

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 鈭?30 and 鈭?0 upstream of the transcription start site of the MIE gene as the 鈥淐REB1 responsive region鈥? Mutations of SP1/3 and NF-魏B 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.