Chicken bromodomain-containing protein 2 interacts with the Newcastle disease virus matrix protein and promotes viral re
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RESEARCH ARTICLE
Open Access
Chicken bromodomain‑containing protein 2 interacts with the Newcastle disease virus matrix protein and promotes viral replication Zhiqiang Duan1,2* , Yifan Han2, Lei Zhou2, Chao Yuan2, Yanbi Wang2, Caiqin Zhao2, Hong Tang2 and Jiaqi Chen2
Abstract Bromodomain-containing protein 2 (BRD2) is a nucleus-localized serine-threonine kinase that plays pivotal roles in the transcriptional control of diverse genes. In our previous study, the chicken BRD2 (chBRD2) protein was found to interact with the Newcastle disease virus (NDV) matrix (M) protein using a yeast two-hybrid screening system, but the role of the chBRD2 protein in the replication of NDV remains unclear. In this study, we first confirmed the interaction between the M protein and chBRD2 protein using fluorescence co-localization, co-immunoprecipitation and pull-down assays. Intracellular binding studies indicated that the C-terminus (aa 264–313) of the M protein and the extra-terminal (ET) domain (aa 619–683) of the chBRD2 protein were responsible for interactions with each other. Interestingly, although two amino acids (T621 and S649) found in the chBRD2/ET domain were different from those in the human BRD2/ET domain and in that of other mammals, they did not disrupt the BRD2-M interaction or the chBRD2-M interaction. In addition, we found that the transcription of the chBRD2 gene was obviously decreased in both NDV-infected cells and pEGFP-M-transfected cells in a dose-dependent manner. Moreover, small interfering RNA-mediated knockdown of chBRD2 or overexpression of chBRD2 remarkably enhanced or reduced NDV replication by upregulating or downregulating viral RNA synthesis and transcription, respectively. Overall, we demonstrate for the first time that the interaction of the M protein with the chBRD2 protein in the nucleus promotes NDV replication by downregulating chBRD2 expression and facilitating viral RNA synthesis and transcription. These results will provide further insight into the biological functions of the M protein in the replication of NDV. Keywords: Newcastle disease virus, matrix protein, bromodomain-containing protein 2, viral replication Introduction Newcastle disease (ND) is an important avian infectious viral disease that causes neurological, respiratory, and gastrointestinal symptoms in poultry and may lead to devastating losses in the poultry industry worldwide [1]. The causative agent of ND is Newcastle disease virus (NDV), also known as avian paramyxovirus type 1, which *Correspondence: [email protected] 1 Key Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountainous Region, Ministry of Education, Guizhou University, Guiyang, China Full list of author information is available at the end of the article
belongs to the genus Orthoavulavirus of the subfamily Paramyxoviridae [2]. The genome of NDV is a nonsegmented, negative-sense, single-stranded RNA that encodes eight proteins, including six structural proteins [the nucleocapsid protein (NP), phosphoprotein protein (P), matrix prote
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