Anthrax toxin receptor 1 is the cellular receptor for Seneca Valley virus Academic Article uri icon

Overview

MeSH Major

  • Capsid Proteins
  • Neoplasm Proteins
  • Picornaviridae
  • Receptors, Cell Surface
  • Receptors, Virus

abstract

  • Seneca Valley virus (SVV) is an oncolytic picornavirus with selective tropism for neuroendocrine cancers. It has shown promise as a cancer therapeutic in preclinical studies and early-phase clinical trials. Here, we have identified anthrax toxin receptor 1 (ANTXR1) as the receptor for SVV using genome-wide loss-of-function screens. ANTXR1 is necessary for permissivity in vitro and in vivo. However, robust SVV replication requires an additional innate immune defect. We found that SVV interacts directly and specifically with ANTXR1, that this interaction is required for SVV binding to permissive cells, and that ANTXR1 expression is necessary and sufficient for infection in cell lines with decreased expression of antiviral IFN genes at baseline. Finally, we identified the region of the SVV capsid that is responsible for receptor recognition using cryoelectron microscopy of the SVV-ANTXR1-Fc complex. These studies identify ANTXR1, a class of receptor that is shared by a mammalian virus and a bacterial toxin, as the cellular receptor for SVV.

publication date

  • August 2017

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5531414

Digital Object Identifier (DOI)

  • 10.1172/JCI93472

PubMed ID

  • 28650343

Additional Document Info

start page

  • 2957

end page

  • 2967

volume

  • 127

number

  • 8