engleski

Differential susceptibility of RAE-1 isoforms to murine cytomegalovirus

NKG2D receptor is one of the most potent activating NK cell receptors involved in antiviral responses. NKG2D ligands in mouse are MULT-1, H60 and RAE-1 family of proteins. We and others have characterized several murine cytomegalovirus (MCMV) proteins involved in the down-modulation of NKG2D ligands. Among these, the gp40 encoded by m152 gene, originally described for its ability to block the maturation of MHC I molecules was also involved in down-modulation of RAE-1 proteins. Based on our initial observations suggesting that in some mouse strains the NKG2D-dependent control is preserved even in response to wild type MCMV, we postulated that there must be NKG2D ligands that resist the virus mediated down-modulation. Here we show that the RAE-1 proteins differ in their susceptibility to the down-regulation by MCMV due to intrinsic differences in stability of the mature surface-expressed protein. In contrast to RAE-1gamma, representing the sensitive isoform, RAE-1delta remains present on the surface of MCMV-infected cells. However, although unable to affect the mature RAE-1delta form, m152 retains the newly synthesized RAE-1delta as well as RAE-1gamma in the endoplasmic reticulum. The different stabilities of RAE-1 isoforms during MCMV infection can be attributed to the absence of the PLWY motif from RAE-1delta.

MCMV; NKG2D; RAE-1; immunoevasion

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