Structural basis for anthrax toxin receptor 1 recognition by Seneca Valley Virus

Area of Science:

• Structural biology
• Virology
• Cancer therapy

Background:

• Oncolytic viruses are emerging as a viable cancer treatment.
• Seneca Valley Virus (SVV) is a promising oncolytic agent.
• Anthrax toxin receptor 1 (ANTXR1) is the identified receptor for SVV.

Purpose of the Study:

• To determine the near-atomic resolution structure of the SVV-ANTXR1 complex.
• To elucidate the molecular interactions between SVV and its receptor ANTXR1.
• To understand the basis for SVV's selective binding to ANTXR1.

Main Methods:

• Single-particle cryo-electron microscopy (cryo-EM) was used to determine the complex structure.
• Comparative analysis of receptor-bound and native SVV capsid structures was performed.
• Molecular interactions at the interface of SVV and ANTXR1 were analyzed.

Main Results:

• The structure of the SVV-ANTXR1 complex was resolved at near-atomic resolution.
• ANTXR1 binds to specific sites on the SVV capsid, including loops and knobs on viral proteins (VP1, VP2, VP3).
• Receptor binding induces minimal conformational changes in the SVV capsid, indicating ANTXR1's role as an attachment receptor.

Conclusions:

• The study provides a detailed structural mechanism for SVV binding to ANTXR1.
• The findings highlight a shared receptor between a virus and a bacterial toxin.
• The structural basis for SVV's selective binding to ANTXR1 over ANTXR2 is explained, offering insights for oncolytic virus design.