NK cell activation through the NKG2D ligand MULT-1 is selectively prevented by the glycoprotein encoded by mouse cytomegalovirus gene m145.
The NK cell-activating receptor NKG2D interacts with three different cellular ligands, all of which are regulated by mouse cytomegalovirus (MCMV). We set out to define the viral gene product regulating murine UL16-binding protein-like transcript (MULT)-1, a newly described NKG2D ligand. We show that MCMV infection strongly induces MULT-1 gene expression, but surface expression of this glycoprotein is nevertheless completely abolished by the virus. Screening a panel of MCMV deletion mutants defined the gene m145 as the viral regulator of MULT-1. The MCMV m145-encoded glycoprotein turned out to be necessary and sufficient to regulate MULT-1 by preventing plasma membrane residence of MULT-1. The importance of MULT-1 in NK cell regulation in vivo was confirmed by the attenuating effect of the m145 deletion that was lifted after NK cell depletion. Our findings underline the significance of escaping MULT-1/NKG2D signaling for viral survival and maintenance.
Krmpotic
Astrid
A
Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
Hasan
Milena
M
Loewendorf
Andrea
A
Saulig
Tanja
T
Halenius
Anne
A
Lenac
Tihana
T
Polic
Bojan
B
Bubic
Ivan
I
Kriegeskorte
Anja
A
Pernjak-Pugel
Ester
E
Messerle
Martin
M
Hengel
Hartmut
H
Busch
Dirk H
DH
Koszinowski
Ulrich H
UH
Jonjic
Stipan
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003587:Cytomegalovirus / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D009154:Mutation; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D020539:Sequence Analysis, Protein; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; C527086:Klrk1 protein, mouse; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C468260:UL16 binding protein 1, mouse; D014764:Viral Proteins