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一株新型猪捷申病毒2的分离与鉴定:PERK介导的未折叠蛋白反应不完全支持病毒复制

Isolation and Characterization of a Novel Porcine Teschovirus 2 Strain: Incomplete PERK-Mediated Unfolded Protein Response Supports Viral Replication.

作者信息

Feng Xiaoying, Du Yiyang, Lv Yueqing, Wei Xiaofang, Cui Chang, Qin Yibin, Lu Bingxia, Chen Zhongwei, Ouyang Kang, Chen Ying, Wei Zuzhang, Huang Weijian, He Ying, Qin Yifeng

机构信息

Laboratory of Animal Infectious Diseases and Molecular Immunology, College of Animal Science and Technology, Guangxi University, Nanning 530004, China.

Guangxi Zhuang Autonomous Region Engineering Research Center of Veterinary Biologics, Guangxi University, Nanning 530004, China.

出版信息

Viruses. 2025 Aug 31;17(9):1200. doi: 10.3390/v17091200.

Abstract

Porcine Teschovirus (PTV) is a highly prevalent pathogen within swine populations, primarily associated with encephalitis, diarrhea, pneumonia, and reproductive disorders in pigs, thereby posing a significant threat to the sustainable development of the pig farming industry. In this study, a novel strain of PTV was isolated from the feces of a pig exhibiting symptoms of diarrhea, utilizing PK-15 cell lines. The structural integrity of the viral particles was confirmed via transmission electron microscopy, and the viral growth kinetics and characteristics were evaluated in PK-15 cells. High-throughput sequencing facilitated the acquisition of the complete viral genome, and subsequent phylogenetic analysis and full-genome alignment identified the strain as belonging to the PTV 2 genotype. Further investigation revealed that infection with the PTV-GXLZ2024 strain induces phosphorylation of the eukaryotic translation initiation factor 2α (eIF2α) in PK-15 cells, indicating activation of the unfolded protein response (UPR) through the PERK pathway, with minimal involvement of the IRE1 or ATF6 pathways. Notably, ATF4 protein expression was progressively downregulated throughout the infection, while downstream CHOP protein levels remained unchanged, indicating an incomplete UPR induced by PTV-GXLZ2024. Furthermore, PERK knockdown was found to enhance the replication of PTV-GXLZ2024. This study provides critical insights into the molecular mechanisms underlying PTV pathogenesis and establishes a foundation for future research into its evolutionary dynamics and interactions with host organisms.

摘要

猪捷申病毒(PTV)是猪群中一种高度流行的病原体,主要与猪的脑炎、腹泻、肺炎和生殖障碍有关,从而对养猪业的可持续发展构成重大威胁。在本研究中,利用PK-15细胞系从一头出现腹泻症状的猪的粪便中分离出一株新型PTV毒株。通过透射电子显微镜确认了病毒颗粒的结构完整性,并在PK-15细胞中评估了病毒的生长动力学和特性。高通量测序有助于获得完整的病毒基因组,随后的系统发育分析和全基因组比对确定该毒株属于PTV 2基因型。进一步研究发现,PTV-GXLZ2024毒株感染可诱导PK-15细胞中真核翻译起始因子2α(eIF2α)磷酸化,表明通过PERK途径激活了未折叠蛋白反应(UPR),而IRE1或ATF6途径的参与极少。值得注意的是,在整个感染过程中,ATF4蛋白表达逐渐下调,而下游CHOP蛋白水平保持不变,表明PTV-GXLZ2024诱导了不完全的UPR。此外,发现敲低PERK可增强PTV-GXLZ2024的复制。本研究为PTV发病机制的分子机制提供了关键见解,并为其进化动态及其与宿主生物体相互作用的未来研究奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/051b/12474445/d2fd1ede755d/viruses-17-01200-g001.jpg

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