Cryo-EM structure of Seneca Valley Virus-Anthrax Toxin Receptor 1 complex

Abstract

Recently, use of oncolytic viruses in cancer therapy has become a realistic therapeutic option. Seneca Valley Virus (SVV) is a newly discovered picornavirus, which has earned a significant reputation as a potent oncolytic agent. Anthrax toxin receptor 1 (ANTXR1), one of cellular receptors for protective antigen secreted by Bacillus anthracis, has been identified as high-affinity cellular receptor for SVV. Here, we report structure of SVV-ANTXR1 complex determined by single-particle cryo-electron microscopy analysis at near-atomic resolution. This is an example of a shared receptor structure between a mammalian virus and a bacterial toxin. Our structure shows that ANTXR1 decorates outer surface of SVV capsid and interacts with surface-exposed BC loop and loop II of VP1, the puff of VP2 and the knob of VP3. Comparison of receptor-bound capsid structure with native capsid structure reveals that receptor binding induces minor conformational changes in SVV capsid structure, suggesting role of ANTXR1 as an attachment receptor. Furthermore, our results demonstrate that capsid footprint on receptor is not conserved in anthrax toxin receptor 2 (ANTXR2), thereby providing a molecular mechanism for explaining exquisite selectivity of SVV for ANTXR1.