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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.

,1
Tihana Lenac,1
Ronald Antulov,1
Bojan Poli
,1
Zsolt Ruzsics,2
Leonidas N. Carayannopoulos,3
Ulrich H. Koszinowski,2
Astrid Krmpoti
,1 and
Stipan Jonji
1*
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
, is resistant to downregulation by MCMV and that this escape has functional importance in vivo. Although m152 retained newly synthesized RAE-1
and RAE-1
in the endoplasmic reticulum, no viral regulator was able to affect the mature RAE-1
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
compared to RAE-1
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
. Altogether, these findings provide evidence for a novel mechanism of host escape from viral immunoevasion of NKG2D-dependent control.
Published ahead of print on 3 June 2009.
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