Identification of porcine PARP11 as a restricted factor for pseudorabies virus.

IF 4.6 2区 医学 Q2 IMMUNOLOGY Frontiers in Cellular and Infection Microbiology Pub Date : 2024-10-09 eCollection Date: 2024-01-01 DOI:10.3389/fcimb.2024.1414827
Chunyun Qi, Dehua Zhao, Xi Wang, Lanxin Hu, Yao Wang, Heyong Wu, Feng Li, Jian Zhou, Tianyi Zhang, Aosi Qi, Yuran Huo, Qiuse Tu, Shuyu Zhong, Hongming Yuan, Dongmei Lv, Shouqing Yan, Hongsheng Ouyang, Daxin Pang, Zicong Xie
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Abstract

Introduction: PRV infection in swine can cause devastating disease and pose a potential threat to humans. Advancing the interplay between PRV and host is essential to elucidate the pathogenic mechanism of PRV and identify novel anti-PRV targets.

Methods: PARP11-KO PK-15 cells were firstly constructed by CRISPR/Cas9 technology. Next, the effect of PARP11-KO on PRV infection was determined by RT-qPCR, TCID50 assay, RNA-seq, and western blot.

Results and discussion: In this study, we identified PARP11 as a host factor that can significantly affect PRV infection. Inhibition of PARP11 and knockout of PARP11 can significantly promoted PRV infection. Subsequently, we further found that PARP11 knockout upregulated the transcription of NXF1 and CRM1, resulting in enhanced transcription of viral genes. Furthermore, we also found that PARP11 knockout could activate the autophagy pathway and suppress the mTOR pathway during PRV infection. These findings could provide insight into the mechanism in which PARP11 participated during PRV infection and offer a potential target to develop anti-PRV therapies.

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鉴定猪 PARP11 为伪狂犬病毒的限制因子。
导言:猪感染 PRV 可导致毁灭性疾病,并对人类构成潜在威胁。研究 PRV 与宿主之间的相互作用对于阐明 PRV 的致病机制和确定新型抗 PRV 靶点至关重要:方法:首先利用CRISPR/Cas9技术构建了PARP11-KO PK-15细胞。方法:首先通过 CRISPR/Cas9 技术构建 PARP11-KO PK-15 细胞,然后通过 RT-qPCR、TCID50 检测、RNA-seq 和 western blot 等方法测定 PARP11-KO 对 PRV 感染的影响:本研究发现,PARP11是一种能显著影响PRV感染的宿主因子。抑制 PARP11 和敲除 PARP11 可显著促进 PRV 感染。随后,我们进一步发现,PARP11基因敲除会上调NXF1和CRM1的转录,从而导致病毒基因的转录增强。此外,我们还发现,在PRV感染过程中,PARP11敲除可激活自噬通路,抑制mTOR通路。这些发现有助于深入了解PARP11在PRV感染过程中的参与机制,并为开发抗PRV疗法提供了潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.90
自引率
7.00%
发文量
1817
审稿时长
14 weeks
期刊介绍: Frontiers in Cellular and Infection Microbiology is a leading specialty journal, publishing rigorously peer-reviewed research across all pathogenic microorganisms and their interaction with their hosts. Chief Editor Yousef Abu Kwaik, University of Louisville is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. Frontiers in Cellular and Infection Microbiology includes research on bacteria, fungi, parasites, viruses, endosymbionts, prions and all microbial pathogens as well as the microbiota and its effect on health and disease in various hosts. The research approaches include molecular microbiology, cellular microbiology, gene regulation, proteomics, signal transduction, pathogenic evolution, genomics, structural biology, and virulence factors as well as model hosts. Areas of research to counteract infectious agents by the host include the host innate and adaptive immune responses as well as metabolic restrictions to various pathogenic microorganisms, vaccine design and development against various pathogenic microorganisms, and the mechanisms of antibiotic resistance and its countermeasures.
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