CCAAT/enhancer binding proteins play a role in oriLyt-dependent genome replication during MHV-68 de novo infection.
10.1007/s13238-011-1060-z
- Author:
Jing QI
1
;
Danyang GONG
;
Hongyu DENG
Author Information
1. CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Base Sequence;
CCAAT-Enhancer-Binding Proteins;
genetics;
metabolism;
Cell Line;
Chromatin Immunoprecipitation;
Cricetinae;
DNA Replication;
DNA, Viral;
chemistry;
genetics;
metabolism;
Electrophoretic Mobility Shift Assay;
Genome, Viral;
Herpesviridae Infections;
genetics;
metabolism;
virology;
Humans;
Mice;
Molecular Sequence Data;
Plasmids;
Promoter Regions, Genetic;
Protein Isoforms;
genetics;
metabolism;
Replication Origin;
Rhadinovirus;
genetics;
metabolism;
Viral Proteins;
genetics;
metabolism;
Virus Latency;
genetics
- From:
Protein & Cell
2011;2(6):463-469
- CountryChina
- Language:English
-
Abstract:
Murine gammaherpesvirus 68 (MHV-68), a member of the gammaherpesvirus family, replicates robustly in permissive cell lines and is able to infect laboratory mice. MHV-68 has emerged as a model for studying the basic aspects of viral replication and host-virus interactions of its human counterparts. Herpesvirus genome replication is mediated through a cis-element in the viral genome called the origin of lytic replication (oriLyt). A family of transcription factors, CCAAT/enhancer binding proteins (C/EBPs), assists in oriLyt-mediated DNA replication during gammaherpesvirus reactivation. In this study, we examined the role of C/EBPs in gammaherpesvirus DNA replication during de novo infection, using MHV-68 as a model. We found that C/EBP α and β bind to the CCAAT boxes in the MHV-68 oriLyt core region both in vitro and in vivo, as demonstrated by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. A dominant negative form of C/EBPs significantly impaired the lytic replication efficiency of MHV-68 on both the plasmid and genome levels in a replication assay, indicating that functional C/EBPs are required for maximal MHV-68 genome DNA replication. Collectively, our data demonstrate that C/EBPs interact with the oriLyt core region and play an important role in MHV-68 lytic DNA replication during de novo infection.