Altered NKp46 Recognition and Elimination of Influenza B Viruses
Alexandra Duev-Cohen,
Batya Isaacson,
Orit Berhani,
Yoav Charpak-Amikam,
Nehemya Friedman,
Yaron Drori,
Michal Mandelboim,
Ofer Mandelboim
Affiliations
Alexandra Duev-Cohen
The Concern Foundation Laboratories at the Lautenberg Center for Immunology and Cancer Research, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel
Batya Isaacson
The Concern Foundation Laboratories at the Lautenberg Center for Immunology and Cancer Research, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel
Orit Berhani
The Concern Foundation Laboratories at the Lautenberg Center for Immunology and Cancer Research, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel
Yoav Charpak-Amikam
The Concern Foundation Laboratories at the Lautenberg Center for Immunology and Cancer Research, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel
Nehemya Friedman
Central Virology Laboratory, Ministry of Health, Public Health Services, Chaim Sheba Medical Center, Tel Hashomer, Ramat-Gan 5265601, Israel
Yaron Drori
Central Virology Laboratory, Ministry of Health, Public Health Services, Chaim Sheba Medical Center, Tel Hashomer, Ramat-Gan 5265601, Israel
Michal Mandelboim
Central Virology Laboratory, Ministry of Health, Public Health Services, Chaim Sheba Medical Center, Tel Hashomer, Ramat-Gan 5265601, Israel
Ofer Mandelboim
The Concern Foundation Laboratories at the Lautenberg Center for Immunology and Cancer Research, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel
Every year, millions of people worldwide are infected with influenza, causing enormous health and economic problems. The most common type of influenza is influenza A. It is known that Natural Killer (NK) cells play an important role in controlling influenza A infection, mostly through the recognition of the viral protein hemagglutinin (HA) by the activating receptor, NKp46. In contrast, little is known regarding NK cell recognition of influenza B viruses, even though they are responsible for a third of all pediatric influenza deaths and are therefore included in the seasonal vaccine each year. Here we show that NKp46 also recognizes influenza B viruses. We show that NKp46 binds the HA protein of influenza B in a sialic acid-dependent manner, and identified the glycosylated residue in NKp46, which is critical for this interaction. We discovered that this interaction has a binding affinity approximately seven times lower than NKp46 binding of influenza A’s HA. Finally, we demonstrated, using mice deficient for the mouse orthologue of NKp46, named NCR1, that NKp46 is not important for influenza B elimination. These findings enable us to better understand the interactions between the different influenza viruses and NK cells that are known to be crucial for viral elimination.
