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猪捷申病毒的VP1蛋白通过阻断MDA5激活来抑制对病毒感染的天然免疫反应。

The VP1 Protein of Porcine Teschovirus Inhibits the Innate Immune Response to Viral Infection by Blocking MDA5 Activation.

作者信息

Li Yuying, Zhang Xinyu, Zhao Baopeng, Zhao Chenchen, Lei Xiaoxiao, Huang Haixin, Li Chengkai, Zheng Min, Lan Tian, Sun Wenchao, Lu HuiJun

机构信息

College of Animal Sciences, Institute of Preventive Veterinary Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, China.

Institute of Virology, Wenzhou University, Wenzhou, Zhejiang 325035, China.

出版信息

Transbound Emerg Dis. 2024 Jan 8;2024:6649669. doi: 10.1155/2024/6649669. eCollection 2024.

Abstract

Porcine teschovirus (PTV) can cause reproductive dysfunction and respiratory diseases, with high mortality rates for sick pigs. Among Picornaviridae family virus-encoded proteins, the VP1 structural protein is critical for viral immune evasion. However, whether PTV VP1 inhibits the type I interferon (IFN) response remains unknown. Here, it shows that the PTV VP1 protein significantly hinders the activation of NF-B, impairing Sendai virus-induced expression of beta IFN (IFN-). Further studies revealed that VP1 targets and interacts with the MDA5 factor in the RIG-I like receptors pathway. More importantly, the VP1 protein interacts with the caspase activation and recruitment domain and Hel domains of MDA5, blocking IFN- expression. Our findings provide evidence about the VP1 protein of PTV hinders MDA5 activation and may represent a viral mechanism to escape the innate immune response.

摘要

猪捷申病毒(PTV)可导致繁殖功能障碍和呼吸道疾病,病猪死亡率很高。在小核糖核酸病毒科病毒编码的蛋白质中,VP1结构蛋白对病毒免疫逃逸至关重要。然而,PTV VP1是否抑制I型干扰素(IFN)反应仍不清楚。在此研究中,发现PTV VP1蛋白显著阻碍NF-κB的激活,损害仙台病毒诱导的β干扰素(IFN-β)表达。进一步研究表明,VP1靶向RIG-I样受体途径中的MDA5因子并与其相互作用。更重要的是,VP1蛋白与MDA5的半胱天冬酶激活和募集结构域以及Hel结构域相互作用,阻断IFN-β表达。我们的研究结果提供了证据,证明PTV的VP1蛋白阻碍MDA5激活,这可能是病毒逃避先天免疫反应的一种机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9b8/12017125/d6ba917fc1cb/TBED2024-6649669.001.jpg

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