Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus

Tal I. Arnon, Hagit Achdout, Ofer Levi, Gal Markel, Nivin Saleh, Gil Katz, Roi Gazit, Tsufit Gonen-Gross, Jacob Hanna, Efrat Nahari, Angel Porgador, Alik Honigman, Bodo Plachter, Dror Mevorach, Dana G. Wolf, Ofer Mandelboim

Research output: Contribution to journalArticlepeer-review

295 Scopus citations


Human cytomegalovirus, a chief pathogen in immunocompromised people, can persist in a healthy immunocompetent host throughout life without being eliminated by the immune system. Here we show that pp65, the main tegument protein of human cytomegalovirus, inhibited natural killer cell cytotoxicity by an interaction with the activating receptor NKp30. This interaction was direct and specific, leading to dissociation of the linked CD3ζ from NKp30 and, consequently, to reduced killing. Thus, pp65 is a ligand for the NKp30 receptor and demonstrates a unique mechanism by which an intracellular viral protein causes general suppression of natural killer cell cytotoxicity by specific interaction with an activating receptor.

Original languageEnglish
Pages (from-to)515-523
Number of pages9
JournalNature Immunology
Issue number5
StatePublished - 9 Dec 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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