NKp46 recognizes the sigma1 protein of reovirus: Implications for reovirus-based cancer therapy

Yotam Bar-On, Yoav Charpak-Amikam, Ariella Glasner, Batya Isaacson, Alexandra Duev-Cohen, Pinchas Tsukerman, Alexander Varvak, Michal Mandelboim, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The recent approval of oncolytic virus for therapy of melanoma patients has increased the need for precise evaluation of the mechanisms by which oncolytic viruses affect tumor growth. Here we show that the human NK cell-activating receptor NKp46 and the orthologous mouse protein NCR1 recognize the reovirus sigma1 protein in a sialic-acid-dependent manner. We identify sites of NKp46/NCR1 binding to sigma1 and show that sigma1 binding by NKp46/NCR1 leads to NK cell activation in vitro. Finally, we demonstrate that NCR1 activation is essential for reovirus-based therapy in vivo. Collectively, we have identified sigma1 as a novel ligand for NKp46/ NCR1 and demonstrated that NKp46/NCR1 is needed both for clearance of reovirus infection and for reovirus-based tumor therapy.

Original languageAmerican English
Article numbere01045-17
JournalJournal of Virology
Volume91
Issue number19
DOIs
StatePublished - 1 Oct 2017

Bibliographical note

Publisher Copyright:
© 2017 American Society for Microbiology.

Keywords

  • NCR1
  • NK
  • NKp46
  • Reovirus

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