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传染性支气管炎病毒强毒株的 ADRP 结构域不足以赋予弱毒的 Beaudette 株致病性表型。

The ADRP domain from a virulent strain of infectious bronchitis virus is not sufficient to confer a pathogenic phenotype to the attenuated Beaudette strain.

机构信息

The Pirbright Institute, Surrey, UK.

出版信息

J Gen Virol. 2018 Aug;99(8):1097-1102. doi: 10.1099/jgv.0.001098. Epub 2018 Jun 12.

DOI:10.1099/jgv.0.001098
PMID:29893665
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6171709/
Abstract

The replicase gene of the coronavirus infectious bronchitis virus (IBV) encodes 15 non-structural proteins (nsps). Nsp 3 is a multi-functional protein containing a conserved ADP-ribose-1″-phosphatase (ADRP) domain. The crystal structures of the domain from two strains of IBV, M41 (virulent) and Beaudette (avirulent), identified a key difference; M41 contains a conserved triple-glycine motif, whilst Beaudette contains a glycine-to-serine mutation that is predicted to abolish ADRP activity. Although ADRP activity has not been formally demonstrated for IBV nsp 3, Beaudette fails to bind ADP-ribose. The role of ADRP in virulence was investigated by generating rIBVs, based on Beaudette, containing either a restored triple-glycine motif or the complete M41 ADRP domain. Replication in vitro was unaffected by the ADRP modifications and the in vivo phenotype of the rIBVs was found to be apathogenic, indicating that restoration of the triple-glycine motif is not sufficient to restore virulence to the apathogenic Beaudette strain.

摘要

冠状病毒传染性支气管炎病毒（IBV）的复制酶基因编码 15 种非结构蛋白（nsp）。nsp3 是一种多功能蛋白，含有保守的 ADP-核糖-1″-磷酸酶（ADRP）结构域。来自两种 IBV 株（毒力株 M41 和无毒株 Beaudette）的该结构域的晶体结构确定了一个关键差异；M41 含有保守的三甘氨酸基序，而 Beaudette 含有甘氨酸到丝氨酸的突变，预计会破坏 ADRP 活性。尽管尚未正式证明 IBV nsp3 具有 ADRP 活性，但 Beaudette 无法结合 ADP-核糖。通过基于 Beaudette 生成含有恢复的三甘氨酸基序或完整 M41 ADRP 结构域的 rIBV，研究了 ADRP 在毒力中的作用。体外复制不受 ADRP 修饰的影响，并且发现 rIBV 的体内表型是无致病性的，表明恢复三甘氨酸基序不足以使无致病性的 Beaudette 株恢复毒力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9765/6171709/5245927b519b/jgv-99-1097-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9765/6171709/d172b7e17472/jgv-99-1097-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9765/6171709/0fb7ec0053ba/jgv-99-1097-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9765/6171709/5245927b519b/jgv-99-1097-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9765/6171709/d172b7e17472/jgv-99-1097-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9765/6171709/0fb7ec0053ba/jgv-99-1097-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9765/6171709/5245927b519b/jgv-99-1097-g003.jpg

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