Modulation of CD112 by the alphaherpesvirus gD protein suppresses dnam-1-dependent NK cell-mediated lysis of infected cells

Korneel Grauwet, Claudia Cantoni, Monica Parodi, Andrea De Maria, Bert Devriendt, Daniela Pende, Lorenzo Moretta, Massimo Vitale, Herman W. Favoreel

Research output: Contribution to journalArticle


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.

Original languageEnglish
Pages (from-to)16118-16123
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number45
Publication statusPublished - Nov 11 2014



  • CD112
  • DNAM-1
  • Herpes
  • NK
  • Pseudorabies

ASJC Scopus subject areas

  • General
  • Medicine(all)

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