Murine cytomegalovirus major immediate-early protein 3 interacts with cellular and viral proteins in viral DNA replication compartments and is important for early gene activation

被引:25
|
作者
Martinez, Francisco Puerta [1 ]
Cosme, Ruth S. Cruz [1 ]
Tang, Qiyi [1 ]
机构
[1] Ponce Sch Med, RCMI Program, Dept Microbiol, Ponce, PR 00716 USA
来源
JOURNAL OF GENERAL VIROLOGY | 2010年 / 91卷
关键词
MOUSE CYTOMEGALOVIRUS; HISTONE DEACETYLASE; IE2; PROTEIN; EXPRESSION; TRANSCRIPTION; INFECTION; RECRUITMENT; PROMOTER; DYSREGULATION; REACTIVATION;
D O I
10.1099/vir.0.022301-0
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Murine cytomegalovirus (MCMV) immediate-early protein 3 (IE3) is essential for successful viral infection. This study developed MCMVs with an EGFP-fused IE3 gene in order to study IE3 gene expression, subnuclear distribution and biological function, as well as to examine the interaction of IE3 with cellular and viral proteins. The generated viruses included MCMVIE3gfp, in which IE1 was completely removed by the in-frame fusion of exons 3 and 5 and the C terminus of IE3 was tagged with EGFP, and MCMVIE1/3gfp, in which IE1 was kept intact and EGFP was also fused to the C terminus of IE3. Unlike human CMV (HCMV), whose growth was significantly reduced when IE2 (the HCMV homologue of IE3 in MCMV) was tagged with EGFP, MCMVs with IE3-EGFP presented an unchanged replication profile. Using these new constructs, the distribution of IE3 was revealed as well as its interaction with viral and cellular proteins, especially proteins pertaining to DNA replication (M44 and El) and cellular intrinsic defence [promyelocytic leukemia protein and histone deacetylases (HDACs)]. It was also shown that IE3 domains co-localize with DNA replication domains, and IE3 attracted other required proteins into IE3 domains via protein protein interactions. In addition, IE3 was shown to interact with HDAC2 and to eliminate the inhibitory effect of HDAC2 on early viral gene production. Together, these results suggest that IE3 acts as a key protein for viral DNA replication by establishing pre-replication domains via recruitment of the required viral and cellular proteins, and by reducing host defences.
引用
收藏
页码:2664 / 2676
页数:13
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