[HTML][HTML] Anthrax toxin receptor 1 is the cellular receptor for Seneca Valley virus

LA Miles, LN Burga, EE Gardner… - The Journal of …, 2017 - Am Soc Clin Investig
LA Miles, LN Burga, EE Gardner, M Bostina, JT Poirier, CM Rudin
The Journal of clinical investigation, 2017Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation