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口蹄疫病毒在滤泡树突状细胞上的定位和持续诱导中和抗体的产生依赖于与补体受体(CR2/CR1)的结合。

Foot-and-mouth disease virus localisation on follicular dendritic cells and sustained induction of neutralising antibodies is dependent on binding to complement receptors (CR2/CR1).

机构信息

The Pirbright Institute, Woking, United Kingdom.

The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom.

出版信息

PLoS Pathog. 2022 May 5;18(5):e1009942. doi: 10.1371/journal.ppat.1009942. eCollection 2022 May.

Abstract

Previous studies have shown after the resolution of acute infection and viraemia, foot-and-mouth disease virus (FMDV) capsid proteins and/or genome are localised in the light zone of germinal centres of lymphoid tissue in cattle and African buffalo. The pattern of staining for FMDV proteins was consistent with the virus binding to follicular dendritic cells (FDCs). We have now demonstrated a similar pattern of FMDV protein staining in mouse spleens after acute infection and showed FMDV proteins are colocalised with FDCs. Blocking antigen binding to complement receptor type 2 and 1 (CR2/CR1) prior to infection with FMDV significantly reduced the detection of viral proteins on FDCs and FMDV genomic RNA in spleen samples. Blocking the receptors prior to infection also significantly reduced neutralising antibody titres, through significant reduction in their avidity to the FMDV capsid. Therefore, the binding of FMDV to FDCs and sustained induction of neutralising antibody responses are dependent on FMDV binding to CR2/CR1 in mice.

摘要

先前的研究表明,在急性感染和病毒血症消退后,口蹄疫病毒(FMDV)衣壳蛋白和/或基因组定位于牛和非洲野牛淋巴组织生发中心的亮区。FMDV 蛋白的染色模式与病毒与滤泡树突状细胞(FDCs)结合一致。我们现在已经证明,在急性感染后,FMDV 蛋白在小鼠脾脏中也呈现出类似的染色模式,并显示 FMDV 蛋白与 FDC 共定位。在感染 FMDV 之前,阻断抗原与补体受体 2 和 1(CR2/CR1)的结合,可显著降低 FDC 上检测到的病毒蛋白和脾脏样本中 FMDV 基因组 RNA 的数量。在感染前阻断受体也可显著降低中和抗体滴度,因为它们与 FMDV 衣壳的亲和力显著降低。因此,FMDV 与 FDC 的结合和持续诱导中和抗体反应依赖于 FMDV 在小鼠中与 CR2/CR1 的结合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/424a/9113581/a5afec7e56a1/ppat.1009942.g001.jpg

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