The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 19 May 2003. doi:10.1084/jem.20021973
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 181K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lodoen, M.
Right arrow Articles by Lanier, L. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lodoen, M.
Right arrow Articles by Lanier, L. L.
Right arrowPubmed/NCBI databases
*Substance via MeSH
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© Rockefeller University Press, 0022-1007/2003/5/1245 $5.00
The Journal of Experimental Medicine, Volume 197, Number 10, 1245-1253

NKG2D-mediated Natural Killer Cell Protection Against Cytomegalovirus Is Impaired by Viral gp40 Modulation of Retinoic Acid Early Inducible 1 Gene Molecules

Melissa Lodoen1, Kouetsu Ogasawara1, Jessica A. Hamerman1, Hisashi Arase1, Jeffrey P. Houchins2, Edward S. Mocarski3 and Lewis L. Lanier1

1 Department of Microbiology and Immunology, Cancer Research Institute, University of California San Francisco, San Francisco, CA 94143
2 R&D Systems, Minneapolis, MN 55413
3 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305

Address correspondence to Lewis L. Lanier, Department of Microbiology and Immunology, Box 0414, University of California San Francisco, San Francisco, CA 94143. Phone: 415-514-0829; Fax: 415-476-0939; E-mail: lanier{at}itsa.ucsf.edu

Natural killer (NK) cells play a critical role in the innate immune response against cytomegalovirus (CMV) infections. Although CMV encodes several gene products committed to evasion of adaptive immunity, viral modulation of NK cell activity is only beginning to be appreciated. A previous study demonstrated that the mouse CMV m152-encoded gp40 glycoprotein diminished expression of ligands for the activating NK cell receptor NKG2D on the surface of virus-infected cells. Here we have defined the precise ligands that are affected and have directly implicated NKG2D in immune responses to CMV infection in vitro and in vivo. Murine CMV (MCMV) infection potently induced transcription of all five known retinoic acid early inducible 1 (RAE-1) genes (RAE-1{alpha}, RAE-1ß, RAE-1{delta}, RAE-1{varepsilon}, and RAE-1{gamma}), but not H-60. gp40 specifically down-regulated the cell surface expression of all RAE-1 proteins, but not H-60, and diminished NK cell interferon {gamma} production against CMV-infected cells. Consistent with previous findings, a m152 deletion mutant virus ({Delta}m152) was less virulent in vivo than the wild-type Smith strain of MCMV. Treatment of BALB/c mice with a neutralizing anti-NKG2D antibody before infection increased titers of {Delta}m152 virus in the spleen and liver to levels seen with wild-type virus. These experiments demonstrate that gp40 impairs NK cell recognition of virus-infected cells through disrupting the RAE-1–NKG2D interaction.

Key Words: NKG2D • RAE-1 • cytomegalovirus • NK cell • gp40


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS