title: Modulation of CD112 by the alphaherpesvirus gD protein suppresses DNAM-1-dependent NK cell-mediated lysis of infected cells.
abstract: Natural killer (NK) cells are key players in the innate response to viruses, including herpesviruses. In particular, the variety of viral strategies to modulate the recognition of certain herpesviruses witnesses the importance of NK cells in the control of this group of viruses. Still, NK evasion strategies have remained largely elusive for the largest herpesvirus subfamily, the alphaherpesviruses. Here, we report that the gD glycoprotein of the alphaherpesviruses pseudorabies virus (PRV) and herpes simplex virus 2 (HSV-2) displays previously uncharacterized immune evasion properties toward NK cells. Expression of gD during infection or transfection led to degradation and consequent down-regulation of CD112, a ligand for the activating NK receptor DNAX accessory molecule 1 (DNAM-1). CD112 downregulation resulted in a reduced ability of DNAM-1 to bind to the surface of both virus-infected and gD-transfected cells. Consequently, expression of gD suppressed NK cell degranulation and NK cell-mediated lysis of PRV- or HSV-2-infected cells. These data identify an alphaherpesvirus evasion strategy from NK cells and point out that interactions between viral envelope proteins and host cell receptors can have biological consequences that stretch beyond virus entry.
authors.affiliation: Laboratory of Immunology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium;
authors.forename: Korneel
authors.initials: K
authors.lastname: Grauwet
authors.affiliation: Department of Experimental Medicine, University of Genova, 16132 Genova, Italy; Center of Excellence for Biomedical Research, University of Genova, 16132 Genova, Italy; Istituto Giannina Gaslini, 16147 Genova, Italy;
authors.forename: Claudia
authors.initials: C
authors.lastname: Cantoni
authors.affiliation: Department of Experimental Medicine, University of Genova, 16132 Genova, Italy;
authors.forename: Monica
authors.initials: M
authors.lastname: Parodi
authors.affiliation: Center of Excellence for Biomedical Research, University of Genova, 16132 Genova, Italy; Laboratory of Immunology, Department of Integrated Oncologic Therapies, Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera Universitaria San Martino-IST Genova, 16132 Genova, Italy; and Department of Health Sciences, University of Genova, 16132 Genova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: De Maria
authors.affiliation: Laboratory of Immunology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium;
authors.forename: Bert
authors.initials: B
authors.lastname: Devriendt
authors.affiliation: Laboratory of Immunology, Department of Integrated Oncologic Therapies, Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera Universitaria San Martino-IST Genova, 16132 Genova, Italy; and.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pende
authors.affiliation: Istituto Giannina Gaslini, 16147 Genova, Italy;
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.affiliation: Laboratory of Immunology, Department of Integrated Oncologic Therapies, Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera Universitaria San Martino-IST Genova, 16132 Genova, Italy; and.
authors.forename: Massimo
authors.initials: M
authors.lastname: Vitale
authors.affiliation: Laboratory of Immunology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium; Herman.Favoreel@UGent.be.
authors.forename: Herman W
authors.initials: HW
authors.lastname: Favoreel
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000235:genetics / Q000276:immunology; D006558:Herpes Genitalis / Q000235:genetics / Q000276:immunology*; D011558:Herpesvirus 1, Suid / Q000235:genetics / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D053646:Interleukin-2 Receptor beta Subunit; D007694:Killer Cells, Natural; D008297:Male; D011557:Pseudorabies / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; C508020:IL2RB protein, human; D053646:Interleukin-2 Receptor beta Subunit; D014759:Viral Envelope Proteins
keywords: CD112; DNAM-1; NK; herpes; pseudorabies