Abstract
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 CD3zeta 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cells, Cultured
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Cytomegalovirus / physiology*
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Cytotoxicity, Immunologic / drug effects
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Gene Expression Regulation
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Humans
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Immunoglobulin Fc Fragments / immunology
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Kinetics
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Membrane Glycoproteins / antagonists & inhibitors*
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Membrane Glycoproteins / metabolism
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Mice
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Natural Cytotoxicity Triggering Receptor 3
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Phosphoproteins / metabolism*
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Phosphoproteins / pharmacology
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Protein Binding
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Receptors, Cell Surface / antagonists & inhibitors
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Receptors, Cell Surface / metabolism
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Receptors, Immunologic / antagonists & inhibitors*
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Receptors, Immunologic / metabolism
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Viral Matrix Proteins / metabolism*
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Viral Matrix Proteins / pharmacology
Substances
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Immunoglobulin Fc Fragments
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Membrane Glycoproteins
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NCR3 protein, human
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Natural Cytotoxicity Triggering Receptor 3
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Phosphoproteins
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Receptors, Cell Surface
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Receptors, Immunologic
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Viral Matrix Proteins
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cytomegalovirus matrix protein 65kDa