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鸡传染性贫血病毒(CIAV)VP1 通过抑制 TBK1 磷酸化来拮抗 I 型干扰素(IFN-I)的产生。

Chicken infectious anemia virus (CIAV) VP1 antagonizes type I interferon (IFN-I) production by inhibiting TBK1 phosphorylation.

机构信息

National Key Laboratory of Veterinary Public Health Security; Key Laboratory of Animal Epidemiology of the Ministry of Agriculture; College of Veterinary Medicine, China Agricultural University, #2 Yuan-Ming-Yuan West Road, Beijing 100193, China.

College of Veterinary Medicine, China Agricultural University, #2 Yuan-Ming-Yuan West Road, Beijing 100193, China.

出版信息

Virus Res. 2023 Apr 2;327:199077. doi: 10.1016/j.virusres.2023.199077. Epub 2023 Feb 22.

Abstract

Chicken infectious anemia virus (CIAV) infection induces immunosuppression or subclinical immunosuppression in chickens. CIAV infection has been reported to repress type I interferon (IFN-I) expression, but the underlying mechanisms are not yet understood. Here we reported that VP1, the capsid protein of CIAV, the major immunogenic protein that triggers the production of neutralizing antibodies in chickens, inhibited type I interferon (IFN-I) expression induced by cGAS-STING signaling. We showed that VP1 inhibited TBK1 phosphorylation and down stream signal transduction, leading to the inhibition of IFN-I expression. Subsequently, we demonstrated that VP1 interacted with TBK1. Finally, we clarified that aa 120-150 in VP1 was essential for VP1 to interact with TBK1 and inhibit cGAS-STING signaling. These findings will help us further understand the pathogenesis of CIAV in chickens.

摘要

鸡传染性贫血病毒(CIAV)感染会导致鸡的免疫抑制或亚临床免疫抑制。据报道,CIAV 感染会抑制 I 型干扰素(IFN-I)的表达,但具体机制尚不清楚。本研究报道,CIAV 的衣壳蛋白 VP1 可抑制 cGAS-STING 信号诱导的 I 型干扰素(IFN-I)表达,VP1 是 CIAV 的主要免疫原性蛋白,可触发鸡体内中和抗体的产生。研究表明,VP1 抑制 TBK1 磷酸化及其下游信号转导,从而抑制 IFN-I 的表达。进一步研究发现,VP1 与 TBK1 相互作用。最后,明确了 VP1 中的 aa120-150 对于 VP1 与 TBK1 相互作用和抑制 cGAS-STING 信号至关重要。这些发现将有助于我们进一步了解 CIAV 在鸡中的致病机制。

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