This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Arapovic, J.
Right arrow Articles by Jonjic, S.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Arapovic, J.
Right arrow Articles by Jonjic, S.

 Previous Article  |  Next Article 

Journal of Virology, August 2009, p. 8198-8207, Vol. 83, No. 16
0022-538X/09/$08.00+0     doi:10.1128/JVI.02549-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Differential Susceptibility of RAE-1 Isoforms to Mouse Cytomegalovirus{triangledown}

Jurica Arapovic,1 Tihana Lenac,1 Ronald Antulov,1 Bojan Polic,1 Zsolt Ruzsics,2 Leonidas N. Carayannopoulos,3 Ulrich H. Koszinowski,2 Astrid Krmpotic,1 and Stipan Jonjic1*

Department of Histology and Embryology, Medical Faculty University of Rijeka, 51000 Rijeka, Croatia,1 Max von Pettenkofer Institute, LMU, 80336 Munich, Germany,2 Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri 631103

Received 11 December 2008/ Accepted 28 May 2009

The NKG2D receptor is one of the most potent activating natural killer cell receptors involved in antiviral responses. The mouse NKG2D ligands MULT-1, RAE-1, and H60 are regulated by murine cytomegalovirus (MCMV) proteins m145, m152, and m155, respectively. In addition, the m138 protein interferes with the expression of both MULT-1 and H60. We show here that one of five RAE-1 isoforms, RAE-1{delta}, is resistant to downregulation by MCMV and that this escape has functional importance in vivo. Although m152 retained newly synthesized RAE-1{delta} and RAE-1{gamma} in the endoplasmic reticulum, no viral regulator was able to affect the mature RAE-1{delta} form which remains expressed on the surfaces of infected cells. This differential susceptibility to downregulation by MCMV is not a consequence of faster maturation of RAE-1{delta} compared to RAE-1{gamma} but rather an intrinsic property of the mature surface-resident protein. This difference can be attributed to the absence of a PLWY motif from RAE-1{delta}. Altogether, these findings provide evidence for a novel mechanism of host escape from viral immunoevasion of NKG2D-dependent control.


* Corresponding author. Mailing address: Department of Histology and Embryology, Medical Faculty University of Rijeka, 51000 Rijeka, Croatia. Phone: 385 51 651 206. Fax: 385 51 651 176. E-mail: jstipan{at}medri.hr

{triangledown} Published ahead of print on 3 June 2009.


Journal of Virology, August 2009, p. 8198-8207, Vol. 83, No. 16
0022-538X/09/$08.00+0     doi:10.1128/JVI.02549-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.