SARS-CoV-2 B.1.1.7 variant antagonises innate immune activation

This pathway describes the antagonistic effects of the SARS-CoV-2 B.1.1.7 (Alpha) variant on innate immune activation. The pathway is based on Figure 5 from [https://www.biorxiv.org/content/10.1101/2021.06.06.446826v1.full Thorne et al.] SARS-CoV-2 is known to antagonize innate immune activation, and the highly transmissible B.1.1.7 variant does this more effectively by increased RNA synthesis and increased protein expression of key innate immune antagonists, orf9b, orf6 and N: N prevents activation of RNA sensor RIG-1 (DDX58), orf6 inhibits IRF3 nuclear translocation and subsequent type 1 interferon production and orf9b inhibits RNA-sensing by binding to TOM70 (TOMM70). The latter interaction is regulated by phosphorylation of orf9b on Ser53; orf9b that is phosphorylated on Ser53 cannot bind to TOM70.

本路径描述了SARS-CoV-2 B.1.1.7（Alpha）变异株对固有免疫激活的拮抗作用。该路径基于Thorne等人在[https://www.biorxiv.org/content/10.1101/2021.06.06.446826v1.full](https://www.biorxiv.org/content/10.1101/2021.06.06.446826v1.full)发表的图5。已知SARS-CoV-2能够拮抗固有免疫激活，而高度传染性的B.1.1.7变异株通过增加RNA合成及关键固有免疫拮抗剂orf9b、orf6和N蛋白的表达，更为有效地实现这一点。N蛋白阻止RNA传感器RIG-1（DDX58）的激活，orf6通过抑制IRF3的核转位以及随后的I型干扰素的产生来实现抑制，orf9b通过结合TOM70（TOMM70）来抑制RNA的感知。后一相互作用受orf9b在Ser53位点的磷酸化调控；磷酸化在Ser53位点的orf9b无法与TOM70结合。