Full title: The function of the NK killer receptor NKp46 in immunosurveillance of cytomegalovirus and influenza viruses

Grantors: The Ministry of Science, Education and Sports of the Republic of Croatia & the Israel Ministry of Science, Culture and Sport

Grantors' websites: http://public.mzos.hr/Default.aspx?sec=2428

http://www.most.gov.il/English/

Programme: Croatia-Israel Joint Research Programme

Programme websites: http://ra.haifa.ac.il/showpage.asp?Idnn=959&namef=MOST&otkuda=search.asp&order=&view

Duration: 2009-2010

Total funding (Croatian project partner – Center for Proteomics): USD 50.000

Principal Investigators: Stipan Jonjic, Faculty of Medicine University of Rijeka and Ofer Mandelboim, Hadassah Medical School, the Hebrew University Jerusalem, Israel

No. of participants: 2

Brief description:

It is well established in vitro that Natural Killer (NK) cells kill target cells after being triggered via a limited number of NK cell receptors. Additionally, NK cells play an important role in pathogenesis of various diseases. However, cellular ligands which are recognized by most of the NK cell receptors are mostly undefined.

The studies proposed in this project will investigate these critical questions in a combined Croatian-Israeli effort, by studying the in vivo role of NKp46, a major NK cell receptor. NKp46 knockout mice in which NKp46 is replaced by GFP will be used; hence, in addition to deletion of NKp46 in these mice, all NK cells are marked green. The functional role of NKp46 during viral infection including cytomegalovirus (CMV) and avian influenza will be tested in vivo.

Furthermore, the preliminary results have shown that the infection with murine CMV resulted in downregulation of an unknown ligand for NKp46/NCR1. The aim is to discover this NKp46 ligand by combining the efforts of the two groups using the following methods: monoclonal antibodies, affinity chromatography, cDNA libraries and phage display libraries. The first two methods will be used by the Croatian team and the two other methods by the Israeli team. The study will demonstrate for the first time the physiological role of a major NK cell receptor in innate responses against avian influenza and CMV. In addition, the identification of new NKp46 ligands will enable the development of new therapies for the treatment of infectious diseases.