engleski

Differential susceptibility of RAE-1 isoforms to mouse cytomegalovirus

The NKG2D receptor is one of the most potent activating NK cell receptors involved in antiviral responses. Mouse NKG2D ligands, MULT-1, RAE-1 and H60 are regulated by mouse cytomegalovirus (MCMV) proteins m145, m152 and m155, respectively. In addition, the m138 protein interferes with the expression of both MULT-1 and H60. Here we show that one of five RAE-1 isoforms, RAE-1delta, is resistant to down-regulation 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 surface of infected cells. This differential susceptibility to down-regulation by MCMV is not a consequence of faster maturation of RAE-1delta as 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.

NKG2D ligands; MCMV proteins

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