Differential susceptibility of RAE-1 isoforms to mouse cytomegalovirus.
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-1delta, is resistant to downregulation by MCMV and that this escape has functional importance in vivo. Although m152 retained newly synthesized RAE-1delta and RAE-1gamma in the endoplasmic reticulum, no viral regulator was able to affect the mature RAE-1delta 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-1delta compared to RAE-1gamma 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-1delta. Altogether, these findings provide evidence for a novel mechanism of host escape from viral immunoevasion of NKG2D-dependent control.
Arapovic
Jurica
J
Department of Histology and Embryology, University of Rijeka, Croatia.
Lenac
Tihana
T
Antulov
Ronald
R
Polic
Bojan
B
Ruzsics
Zsolt
Z
Carayannopoulos
Leonidas N
LN
Koszinowski
Ulrich H
UH
Krmpotic
Astrid
A
Jonjic
Stipan
S
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D015870:Gene Expression; D006566:Herpesviridae Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D007694:Killer Cells, Natural / Q000276:immunology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018146:Muromegalovirus / Q000235:genetics / Q000276:immunology*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000276:immunology; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
C527086:Klrk1 protein, mouse; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D020033:Protein Isoforms; C491217:Raet1c protein, mouse; C491216:Raet1d, protein, mouse; D014764:Viral Proteins