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C/EBPβ 依赖性诱导 TFDP2 促进猪繁殖与呼吸综合征病毒增殖。

The C/EBPβ-Dependent Induction of TFDP2 Facilitates Porcine Reproductive and Respiratory Syndrome Virus Proliferation.

机构信息

School of Life Sciences, Tianjin University, Tianjin, 300072, China.

Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin University, Tianjin, 300072, China.

出版信息

Virol Sin. 2021 Dec;36(6):1341-1351. doi: 10.1007/s12250-021-00403-w. Epub 2021 Jun 17.

Abstract

Porcine reproductive and respiratory syndrome (PRRS) is an important infectious disease caused by porcine reproductive and respiratory syndrome virus (PRRSV), leading to significant economic losses in swine industry worldwide. Although several studies have shown that PRRSV can affect the cell cycle of infected cells, it is still unclear how it manipulates the cell cycle to facilitate its proliferation. In this study, we analyzed the mRNA expression profiles of transcription factors in PRRSV-infected 3D4/21 cells by RNA-sequencing. The result shows that the expression of transcription factor DP2 (TFDP2) is remarkably upregulated in PRRSV-infected cells. Further studies show that TFDP2 contributes to PRRSV proliferation and the PRRSV nucleocapsid (N) protein induces TFDP2 expression by activating C/EBPβ. TFDP2 positively regulates cyclin A expression and triggers a less proportion of cells in the S phase, which contributes to PRRSV proliferation. This study proposes a novel mechanism by which PRRSV utilizes host protein to regulate the cell cycle to favor its infection. Findings from this study will help us for a better understanding of PRRSV pathogenesis.

摘要

猪繁殖与呼吸综合征(PRRS)是一种由猪繁殖与呼吸综合征病毒(PRRSV)引起的重要传染病,导致全球养猪业遭受重大经济损失。尽管已有多项研究表明 PRRSV 可影响感染细胞的细胞周期,但目前仍不清楚其如何操纵细胞周期以促进自身增殖。在这项研究中,我们通过 RNA 测序分析了 PRRSV 感染的 3D4/21 细胞中转录因子的 mRNA 表达谱。结果表明,PRRSV 感染细胞中转录因子 DP2(TFDP2)的表达显著上调。进一步的研究表明,TFDP2 有助于 PRRSV 的增殖,且 PRRSV 核衣壳(N)蛋白通过激活 C/EBPβ 诱导 TFDP2 表达。TFDP2 正向调节细胞周期蛋白 A 的表达,并使更少比例的细胞进入 S 期,从而促进 PRRSV 的增殖。本研究提出了一种新的机制,即 PRRSV 利用宿主蛋白来调节细胞周期以利于其感染。本研究的结果将有助于我们更好地理解 PRRSV 的发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503d/8692629/d7a74e35f3b0/12250_2021_403_Fig1_HTML.jpg

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