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-γ 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.

Korean mistletoe lectin enhances natural killer cell cytotoxicity via upregulation of perforin expression

“…27 This may be due to the NCR receptor binding affinity for viral glycoproteins. 31 In addition, perforin expression was increased following exposure to KMLC. Resveratrol also upregulates perforin protein in NK cells and activates the MAPK pathway by NKG2D activation.…”

Interaction of Mycobacterium tuberculosis Cell Wall Components with the Human Natural Killer Cell Receptors NKp44 and Toll‐Like Receptor 2

“…NKp30 or NKp46) [38]. Finally, it has been demonstrated that NKp44 interacts with envelope glycoproteins from the West Nile and dengue flaviviruses [31].…”

“…Over the last years, it has become increasingly evident that NK cells can use a third recognition strategy, which relies on direct recognition of pathogens by NK cell receptors with consequent activation of NK cell effector functions [7]. The possible receptors able to directly recognize whole micro-organisms or micro-organism-derived products include several members of the TLR family [13,28], intracellular receptors like NOD2 [29] or members of the NCR family [30,31].…”

Dimerization of NKp46 Receptor Is Essential for NKp46-Mediated Lysis: Characterization of the Dimerization Site by Epitope Mapping

“…NKp30 recognizes the cellular ligands B7-H6, BAT3 (9,10), the HCMV protein pp65 (11), and heparan sulfate (HS) as a co-ligand (12). In contrast, however, the cellular ligands for both NKp44 and NKp46 are largely unknown, and the ligands identified to date for these two proteins are various virus hemagglutinins (13,14), flavivirus E-protein for NKp44 (15) and HS as a co-ligand (12,(16)(17)(18). Vimentin was reported as cellular ligand for NKp46 (19).…”