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一项比较转录组学分析表明,HSP90AB1 参与了猪德尔塔冠状病毒感染的免疫和炎症反应。

A Comparative Transcriptomic Analysis Reveals That HSP90AB1 Is Involved in the Immune and Inflammatory Responses to Porcine Deltacoronavirus Infection.

机构信息

Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.

Sichuan Science-Observation Experimental Station for Veterinary Drugs and Veterinary Diagnostic Technology, Ministry of Agriculture, Chengdu 611130, China.

出版信息

Int J Mol Sci. 2022 Mar 18;23(6):3280. doi: 10.3390/ijms23063280.

Abstract

PDCoV is an emerging enteropathogenic coronavirus that mainly causes acute diarrhea in piglets, seriously affecting pig breeding industries worldwide. To date, the molecular mechanisms of PDCoV-induced immune and inflammatory responses or host responses in LLC-PK cells in vitro are not well understood. HSP90 plays important roles in various viral infections. In this study, HSP90AB1 knockout cells (HSP90AB1) were constructed and a comparative transcriptomic analysis between PDCoV-infected HSP90AB1 and HSP90AB1 cells was conducted using RNA sequencing to explore the effect of HSP90AB1 on PDCoV infection. A total of 1295 and 3746 differentially expressed genes (DEGs) were identified in PDCoV-infected HSP90AB1 and HSP90AB1 cells, respectively. Moreover, most of the significantly enriched pathways were related to immune and inflammatory response-associated pathways upon PDCoV infection. The DEGs enriched in NF-κB pathways were specifically detected in HSP90AB1 cells, and NF-κB inhibitors JSH-23, SC75741 and QNZ treatment reduced PDCoV infection. Further research revealed most cytokines associated with immune and inflammatory responses were upregulated during PDCoV infection. Knockout of HSP90AB1 altered the upregulated levels of some cytokines. Taken together, our findings provide new insights into the host response to PDCoV infection from the transcriptome perspective, which will contribute to illustrating the molecular basis of the interaction between PDCoV and HSP90AB1.

摘要

PDCoV 是一种新兴的肠道致病性冠状病毒,主要导致仔猪急性腹泻,严重影响全球养猪业。迄今为止,PDCoV 诱导的免疫和炎症反应或体外 LLC-PK 细胞中宿主反应的分子机制尚不清楚。HSP90 在各种病毒感染中发挥重要作用。在这项研究中,构建了 HSP90AB1 敲除细胞(HSP90AB1),并使用 RNA 测序对 PDCoV 感染的 HSP90AB1 和 HSP90AB1 细胞进行了比较转录组分析,以探讨 HSP90AB1 对 PDCoV 感染的影响。在 PDCoV 感染的 HSP90AB1 和 HSP90AB1 细胞中分别鉴定出 1295 和 3746 个差异表达基因(DEGs)。此外,大多数显著富集的途径与 PDCoV 感染后的免疫和炎症反应相关途径有关。在 HSP90AB1 细胞中特异性检测到 NF-κB 途径中富集的 DEGs,并且 NF-κB 抑制剂 JSH-23、SC75741 和 QNZ 处理可降低 PDCoV 感染。进一步研究表明,在 PDCoV 感染过程中,与免疫和炎症反应相关的大多数细胞因子上调。HSP90AB1 的敲除改变了一些细胞因子的上调水平。总之,我们的研究结果从转录组角度提供了宿主对 PDCoV 感染反应的新见解,这将有助于阐明 PDCoV 与 HSP90AB1 相互作用的分子基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1909/8953809/fb6fabe4a377/ijms-23-03280-g001.jpg

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