2. Academic Validation
  3. Identification of Oncolytic Avian Reovirus Receptors in B16-F10 Cells and the Signaling-Mediated Pathways Involved in Viral Entry

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

  • Viruses. 2026 Mar 12;18(3):350. doi: 10.3390/v18030350.
Chao-Yu Hsu 1,  Bo-Yan Tu 2,  Jyun-Yi Li 2 3,  Tsai-Ling Liao 4 5 6,  Yi-Ying Wu 2 3,  Chia-Ying Lin 7,  Yu-Kang Chang 8,  Muhammad Munir 9,  Hung-Jen Liu 2 3 5 6 10
Affiliations

Affiliations

  • 1 Division of Urology, Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung 435, Taiwan.
  • 2 Institute of Molecular Biology, National Chung Hsing University, Taichung 402, Taiwan.
  • 3 The IEGG and Animal Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan.
  • 4 Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan.
  • 5 Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan.
  • 6 Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan.
  • 7 Department of Beauty Science, Meiho University, Pingtung 912, Taiwan.
  • 8 Department of Medical Research, Tungs' Taichung MetroHarbor Hospital, Taichung 435, Taiwan.
  • 9 Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancashire LA1 4YW, UK.
  • 10 Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan.
PMID: 41902258 DOI: 10.3390/v18030350
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.

Keywords

Plg-RKT receptor; avian reovirus 1; oncolytic virus; virus entry; σC protein.

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