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

Nadishka Jayawardena1, Laura N Burga1, Richard A Easingwood2

  • 1Department of Microbiology and Immunology, University of Otago, 9054 Dunedin, New Zealand.

Proceedings of the National Academy of Sciences of the United States of America
|November 2, 2018
PubMed

Insights

Seneca Valley Virus (SVV), a potent oncolytic virus, binds to Anthrax toxin receptor 1 (ANTXR1). This structural study reveals how SVV uses ANTXR1 for cancer therapy, showing specific binding interactions.

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.
Keywords:
Seneca Valley Viruscancer therapycryo-electron microscopypicornavirusvirus receptor interaction

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