engleski

Most abundant transcript (MAT) of MCMV and its multiple immunoevasion mechanisms

Cytomegaloviruses (CMV) have developed multiple immunoevasion strategies to compromise host’s immune response. One of the strategies involves downregulation of MHC I molecules from the cell surface to prevent T cell response. Since lack of MHC I could activate NK cells via “missing-self” mechanism, MCMV encodes for m04, a protein that binds to some MHC I molecules, escorts them to the cell surface and enables the engagement to inhibitory NK Ly49 receptors. However, some activating Ly49 receptors specifically recognize MHC I-m04 complex together with another viral component and trigger NK cells. We have narrowed down this missing factor to a novel, spliced most abundant transcript (MAT) that encompasses two viral genes, m168-m169. Furthermore, this transcript codes for at least two proteins and contains a binding site for cellular miR-27 (Juranic Lisnic et al. 2013, Marcinowski, Tanguy et al. 2012). Here we show that 5'-UTR region of MAT (uORF MAT) plays a role in the recognition of infected cells by NK through both activating and inhibitory Ly49 receptors. Our results demonstrate that uORF MAT not only affects the level of MHC I on the surface of infected cells and their maturation, but also regulates quality of peptides that are loaded onto MHC I suggesting its potential role in the evasion of T cell recognition. Furthermore, deletion of uORF MAT region of MCMV results in attenuation of the virus in vivo, affects NK cells maturation and activation and IFNγ production.

MCMV; immunoevasion; Ly49 receptors; NK cells

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