title: NKp44 receptor mediates interaction of the envelope glycoproteins from the West Nile and dengue viruses with NK cells.
abstract: Dengue virus (DV) and West Nile virus (WNV) have become a global concern due to their widespread distribution and their ability to cause a variety of human diseases. Antiviral immune defenses involve NK cells. In the present study, we investigated the interaction between NK cells and these two flaviviruses. We show that the NK-activating receptor NKp44 is involved in virally mediated NK activation through direct interaction with the flavivirus envelope protein. Recombinant NKp44 directly binds to purified DV and WNV envelope proteins and specifically to domain III of WNV envelope protein; it also binds to WNV virus-like particles. These WNV-virus-like particles and WNV-domain III of WNV envelope protein directly bind NK cells expressing high levels of NKp44. Functionally, interaction of NK cells with infective and inactivated WNV results in NKp44-mediated NK degranulation. Finally, WNV infection of cells results in increased binding of rNKp44 that is specifically inhibited by anti-WNV serum. WNV-infected target cells induce IFN-gamma secretion and augmented lysis by NKp44-expressing primary NK cells that are blocked by anti-NKp44 Abs. Our findings show that triggering of NK cells by flavivirus is mediated by interaction of NKp44 with the flavivirus envelope protein.
authors.affiliation: Shraga Segal Department of Microbiology and Immunology and National Institute for Biotechnology in the Negev, Ben Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Oren
authors.initials: O
authors.lastname: Hershkovitz
authors.forename: Benyamin
authors.initials: B
authors.lastname: Rosental
authors.forename: Lior Ann
authors.initials: LA
authors.lastname: Rosenberg
authors.forename: Martha Erika
authors.initials: ME
authors.lastname: Navarro-Sanchez
authors.forename: Sergey
authors.initials: S
authors.lastname: Jivov
authors.forename: Alon
authors.initials: A
authors.lastname: Zilka
authors.forename: Orly
authors.initials: O
authors.lastname: Gershoni-Yahalom
authors.forename: Elodie
authors.initials: E
authors.lastname: Brient-Litzler
authors.forename: Hugues
authors.initials: H
authors.lastname: Bedouelle
authors.forename: Joanna W
authors.initials: JW
authors.lastname: Ho
authors.forename: Kerry S
authors.initials: KS
authors.lastname: Campbell
authors.forename: Bracha
authors.initials: B
authors.lastname: Rager-Zisman
authors.forename: Philippe
authors.initials: P
authors.lastname: Despres
authors.forename: Angel
authors.initials: A
authors.lastname: Porgador
mesh_terms: D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D003716:Dengue Virus / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D055629:Natural Cytotoxicity Triggering Receptor 2 / Q000502:physiology*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism*; D014771:Virion / Q000276:immunology; D014902:West Nile virus / Q000276:immunology / Q000378:metabolism*
chemical_list: C112837:NCR2 protein, human; D055629:Natural Cytotoxicity Triggering Receptor 2; D014759:Viral Envelope Proteins