Nuclear localization of Newcastle disease virus matrix protein promotes virus replication by affecting viral RNA synthesis and transcription and inhibiting host cell transcription
Nuclear localization of Newcastle disease virus matrix protein promotes virus replication by affecting viral RNA synthesis and transcription and inhibiting host cell transcription
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新城疫病毒基质蛋白的核定位通过影响病毒RNA合成和转录并抑制宿主细胞转录来促进病毒复制
DOI：
10.1186/s13567-019-0640-4
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发表时间：
2019-03-20
影响因子：
4.4
通讯作者：
Gao, Hongbo
中科院分区：
文献类型：
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作者：
Duan, Zhiqiang;Deng, Shanshan;Gao, Hongbo
副粘病毒蛋白质的核定位对于病毒的生命周期，包括病毒复制的调节和逃避宿主免疫是至关重要的。我们以前的研究表明，重组纽卡斯尔病病毒（NDV）与核定位信号突变的基质（M）蛋白的结果，在致病型的变化和减弱病毒的致病性在鸡。然而，对NDV M蛋白的核定位功能知之甚少。在这项研究中，M蛋白在细胞核中的潜在功能进行了研究。我们首次证明，核定位的M蛋白不仅可以促进NDV的细胞致病性，但也增加了病毒RNA的合成和转录效率在DF-1细胞。使用微阵列分析，我们发现，核定位的M蛋白可能会抑制宿主细胞的转录，代表了许多上调基因与转录抑制活性和下调基因与转录激活活性。然后评估代表性上调基因PROX 1和下调基因AHR在NDV复制中的作用。结果表明，siRNA介导的PROX 1和AHR基因的敲低分别显著降低或增加了NDV的RNA合成和病毒复制，表明这些基因的表达变化在NDV复制中起重要作用。总之，我们的研究结果首次证明，核定位NDV M蛋白促进病毒复制，通过影响病毒RNA的合成和转录，抑制宿主细胞的转录，提高我们的理解NDV复制和发病的分子机制。
Nuclear localization of paramyxovirus proteins is crucial for virus life cycle, including the regulation of viral replication and the evasion of host immunity. We previously showed that a recombinant Newcastle disease virus (NDV) with nuclear localization signal mutation in the matrix (M) protein results in a pathotype change and attenuates viral pathogenicity in chickens. However, little is known about the nuclear localization functions of NDV M protein. In this study, the potential functions of the M protein in the nucleus were investigated. We first demonstrate that nuclear localization of the M protein could not only promote the cytopathogenicity of NDV but also increase viral RNA synthesis and transcription efficiency in DF-1 cells. Using microarray analysis, we found that nuclear localization of the M protein might inhibit host cell transcription, represented by numerous up-regulating genes associated with transcriptional repressor activity and down-regulating genes associated with transcriptional activator activity. The role of representative up-regulated gene prospero homeobox 1 (PROX1) and down-regulated gene aryl hydrocarbon receptor (AHR) in the replication of NDV was then evaluated. The results show that siRNA-mediated knockdown of PROX1 or AHR significantly reduced or increased the viral RNA synthesis and viral replication, respectively, demonstrating the important roles of the expression changes of these genes in NDV replication. Together, our findings demonstrate for the first time that nuclear localization of NDV M protein promotes virus replication by affecting viral RNA synthesis and transcription and inhibiting host cell transcription, improving our understanding of the molecular mechanism of NDV replication and pathogenesis.