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

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 languageEnglish
Article numbere01045-17
JournalJournal of Virology
Volume91
Issue number19
DOIs
StatePublished - 1 Oct 2017

Bibliographical note

Publisher Copyright:
© 2017 American Society for Microbiology.

Funding

This study was supported by the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC (grant agreement number 320473-BacNK). Further support came from the Israel Science Foundation, the GIF Foundation, the Lewis Family Foundation, the ICRF professorship grant, the Helmholtz Israel grant, and the Rosetrees Trust (all to O.M.). Further support came from the I-CORE Program of the Planning and Budgeting Committee and the Israel Science Foundation and from the I-Core on Chromatin and RNA in Gene Regulation. O.M. is a Crown Professor of Molecular Immunology. The funders had no role in study design, data collection and analysis, the decision to publish, or preparation of the manuscript.

FundersFunder number
Helmholtz Israel
I-Core on Chromatin
Lewis Family Foundation
Israel Cancer Research Fund
Seventh Framework ProgrammeFP/2007-2013
Glycemic Index Foundation
European Research Council320473-BacNK
Rosetrees Trust
Israel Science Foundation
Planning and Budgeting Committee of the Council for Higher Education of Israel

    Keywords

    • NCR1
    • NK
    • NKp46
    • Reovirus

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