The Glycophosphatidylinositol Anchor of the MCMV Evasin, m157, Facilitates Optimal Cell Surface Expression and Ly49 Receptor Recognition

Lindsey E Carlin; Natalya V Guseva; Michael R Shey; Zuhair K Ballas; Jonathan W Heusel

doi:10.1371/journal.pone.0067295

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The Glycophosphatidylinositol Anchor of the MCMV Evasin, m157, Facilitates Optimal Cell Surface Expression and Ly49 Receptor Recognition

Journal article

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The Glycophosphatidylinositol Anchor of the MCMV Evasin, m157, Facilitates Optimal Cell Surface Expression and Ly49 Receptor Recognition

Lindsey E Carlin, Natalya V Guseva, Michael R Shey, Zuhair K Ballas and Jonathan W Heusel

PloS one, Vol.8(6), pp.e67295-e67295

2013

DOI: 10.1371/journal.pone.0067295

PMCID: PMC3686720

PMID: 23840655

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Abstract

The murine cytomegalovirus-encoded protein m157 is a cognate ligand for both inhibitory and activating receptors expressed by natural killer cells. Additionally, m157 is expressed on the surface of infected cells by a glycophosphatidylinositol (GPI) anchor. Although endogenous GPI-anchored proteins are known to be ligands for the NK cell receptor, NKG2D, the contribution of the GPI anchor for viral m157 ligand function is unknown. To determine whether the GPI anchor for m157 is dispensable for m157 function, we generated m157 variants expressed as transmembrane fusion proteins and tested cells expressing transmembrane m157 for the capacity to activate cognate Ly49 receptors. We found that the GPI anchor is required for high-level cell surface expression of m157, and that the transmembrane m157 ligand retains the capacity to activate reporter cells and NK cells expressing Ly49H, as well as Ly49I(129) reporter cells, but with reduced potency. Importantly, target cells expressing the transmembrane form of m157 were killed less efficiently and failed to mediate Ly49H receptor downregulation on fresh NK cells compared to targets expressing GPI-anchored m157. Taken together, these results show that the GPI anchor for m157 facilitates robust cell surface expression, and that NK cells are sensitive to the altered cell surface expression of this potent viral evasin.

Muromegalovirus - immunology

NK Cell Lectin-Like Receptor Subfamily A - metabolism

Animals

Glycosylphosphatidylinositols - metabolism

Down-Regulation

Mice, Inbred C57BL

Killer Cells, Natural - immunology

Mice

Viral Proteins - metabolism

Cytotoxicity, Immunologic

Muromegalovirus - metabolism

Details

Title: Subtitle: The Glycophosphatidylinositol Anchor of the MCMV Evasin, m157, Facilitates Optimal Cell Surface Expression and Ly49 Receptor Recognition
Creators: Lindsey E Carlin - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of America ; The Department of Pathology, University of Iowa, Iowa City, Iowa, United States of America
Natalya V Guseva
Michael R Shey
Zuhair K Ballas
Jonathan W Heusel
Resource Type: Journal article
Publication Details: PloS one, Vol.8(6), pp.e67295-e67295
DOI: 10.1371/journal.pone.0067295
PMID: 23840655
PMCID: PMC3686720
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science
Grant note: R56 AI088182 / NIAID NIH HHS R21 AI076989 / NIAID NIH HHS
Language: English
Date published: 2013
Academic Unit: Pathology; Immunology; Internal Medicine
Record Identifier: 9984094764502771

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