免疫调节分子K3L蛋白在羊痘病毒宿主范围差异中的作用及分子机制

批准号:
31972687
项目类别:
面上项目
资助金额:
58.0 万元
负责人:
赵志荀
依托单位:
学科分类:
兽医免疫学
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
赵志荀
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中文摘要
自然条件下,山羊痘病毒(GPV)既感染山羊也感染绵羊,而绵羊痘病毒(SPV)只感染绵羊,目前羊痘病毒宿主范围差异的机制尚不清楚。我们前期研究表明,SPV主要的宿主范围因子K3L能够竞争结合绵羊PKR,阻断其与eIF2a的结合,从而阻断宿主对病毒的抑制。有趣的是,GPV K3L与PKR的结合明显强于SPV K3L与PKR的结合。这指示K3L与PKR结合亲和力强弱差异可能是导致GPV与SPV宿主范围差异的一个重要原因。因此,本项目拟通过SPRi等方法体外测定并比较SPV和GPV的K3L与绵羊/山羊PKR结合亲和力差异;构建SPV和GPV的K3L的关键氨基酸互换、缺失重组病毒,通过噬斑等方法测定它们感染不同细胞后的生长特征差异,通过qPCR和免疫组化等方法测定重组病毒感染绵羊和山羊后的复制水平与组织分布差异,从而明确K3L在羊痘病毒宿主范围差异中的作用。本课题对理解痘病毒免疫逃逸机制有重要意义。
英文摘要
The host range difference mechanism of poxvirus is largely unkown at present.Naturally, goatpox virus (GPV) can infect goats and sheep, but sheeppox virus (SPV) can only infect sheep but not goats. Previous studies showed that the poxvirus host range factor K3L protein can bind with host PKR and inhibit the phosphorylation of PKR, and thus reduced the ability of host inhibition virus replication. After we calculated the interaction energy between PKR and K3L, the results showed that the binding energy between GPV K3L and PKR is stronger than the binding energy between SPV K3L and PKR. Therefore, we suggest that it is possible that the strength of K3L binding with PKR result in host range difference between SPV and GPV. To reveal the mechanism of the host range difference between SPV and GPV, we plan to measure the binding affinity intensity difference between K3L (of SPV and GPV) and PKR (of goat and sheep) using SPRi system in this program. A K3L gene deletion mutant SPV and GPV, as well as exchanged the key amino acid of K3L between SPV and GPV recombinant SPV and GPV will be constructed, and then we will determine their growth characteristics difference for all mutant virus after infected different host cell lines by plaque and real time PCR methods. Finally, after determinate recombinant viral replication level and organization distribution of virus after infected sheep and goats, we can make clear how binding energy between PKR and K3L affect the host range difference between GPV and SPV. This study has important significance for understanding the mechanism of immune escape of poxvirus, and will be helpful for the prevention and control of capripox.
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DOI:10.13345/j.cjb.210164
发表时间:2022-01-01
期刊:Chinese Journal of Biotechnology
影响因子:--
作者:Wang Zhanhong;Zhao Zhixun;Zhang Qiang
通讯作者:Zhang Qiang
DOI:https://doi.org/10.1007/s00253-022-12351-w
发表时间:2022
期刊:Applied Microbiology and Biotechnology
影响因子:--
作者:Zhixun Zhao;Caiyun Huang;Xueliang Zhu;Zheng Qi;Yimei Cao;Pinghua Li;Zaixin Liu;Qiang Zhang;Zengjun Lu
通讯作者:Zengjun Lu
DOI:10.16431/j.cnki.1671-7236.2020.07.003
发表时间:2020
期刊:中国畜牧兽医
影响因子:--
作者:王战红;赵志荀;吴国华;朱学亮;黄彩云;祁斌亮;赵芳燕;张志东;张强
通讯作者:张强
病毒诱导的DNA损伤反应中DNA-PK介导自噬影响病毒复制的分子机制
- 批准号:32372988
- 项目类别:面上项目
- 资助金额:50万元
- 批准年份:2023
- 负责人:赵志荀
- 依托单位:
基于SILAC和磷酸化蛋白组学研究羊痘病毒K3L蛋白在调节宿主PKR信号通路中的作用
- 批准号:31201892
- 项目类别:青年科学基金项目
- 资助金额:23.0万元
- 批准年份:2012
- 负责人:赵志荀
- 依托单位:
国内基金
海外基金
