# Identification of Oncolytic Avian Reovirus Receptors in B16-F10 Cells and the Signaling-Mediated Pathways Involved in Viral Entry

## TL;DR

This study identifies Plg-RKT as a key receptor for avian reovirus entry into melanoma cells and reveals the signaling pathways involved in the process.

## Contribution

The study identifies Plg-RKT as a crucial receptor for avian reovirus entry and uncovers the role of Src-p38 MAPK signaling in viral internalization.

## Key findings

- Plg-RKT is a crucial receptor mediating ARV σC binding and entry into B16-F10 melanoma cells.
- Inhibition of Plg-RKT expression markedly reduces ARV infection.
- ARV binding to Plg-RKT activates Src and p38 MAPK signaling pathways, promoting caveolae-mediated endocytosis.

## Abstract

Avian reovirus (ARV) is a major poultry pathogen recently recognized for its potential as an oncolytic virus that selectively infects and kills cancer cells without harming healthy human cells. However, the receptors mediating ARV entry into cancer cells remain unclear. Using mouse melanoma B16-F10 cells as a model, this study identified ARV-binding receptor candidates through viral overlay protein binding assay (VOPBA), SDS-PAGE, and LC-MS/MS analysis. Plaque-forming assays (PFAs) evaluated viral replication efficiency, while co-immunoprecipitation (Co-IP) and proximity ligation assay (PLA) confirmed direct interactions between viral σC and host receptor proteins. Functional assays using shRNA knockdown and antibody blocking demonstrated that inhibition of Plg-RKT expression markedly reduced ARV infection. Western blot analysis revealed that ARV binding to Plg-RKT activates Src and p38 MAPK signaling pathways, which promote caveolin-1 phosphorylation and caveolae-mediated endocytosis. These findings identify Plg-RKT as a crucial receptor mediating ARV σC binding and entry into B16-F10 melanoma cells. Furthermore, activation of Src-p38 MAPK signaling was shown to be essential for viral internalization. This study elucidates the molecular mechanism underlying ARV entry into melanoma cells and provides valuable insight for improving the selectivity and therapeutic potential of ARV as an oncolytic virus.