engleski

Complex interplay between Ly49 receptors and MCMV

Cytomegaloviruses downregulate MHC I from the cell surface in order to avoid recognition by T cells. Since this strategy could trigger the NK cell-mediated “missing-self” recognition, murine cytomegalovirus (MCMV) encodes m04, a protein which brings a portion of MHC I molecules back to the cell surface enabling them to engage inhibitory Ly49 receptors (iLy49s). Differential sensitivity of various mouse strains to MCMV has been linked to the capacity of NK cells to recognize infected cells via activating Ly49 receptors. In certain cases, Ly49 receptors recognize MHCI, m04 and an additional, 11kDa viral protein encoded by the MCMV’s most abundant transcript (MAT), which also encodes another protein of unknown function and contains a binding site for cellular micro RNA (Marcinowski et al (2012) PLOS Pathogens ; Juranic Lisnic et al (2013) PLOS Pathogens). Here we show that the deletion of MAT results in a modest downregulation of MHC I from the cell surface and drastically changes the repertoire of host and viral peptides presented in MHC I. In addition, viral mutants lacking MAT are attenuated in vivo and their titers can be restored by NK cell depletion.

nk cells; ly49 receptors; mcmv; m04; immunoevasion

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