engleski

''Cytomegalovirus downregulation of PVR reveals strong effect of DNAM-1 in virus control by NK cells and macrophages''

The poliovirus receptor (PVR), or CD155, is a highly conserved and ubiquitously expressed molecule which plays a role in the immune response to tumours and viruses. PVR serves as a ligand for the activating receptor DNAM-1 as well as for inhibitory receptor TIGIT. PVR also binds to CD96 receptor for which both activating and inhibitory functions have been described. DNAM-1 is expressed on the majority of immune cells including NK cells, monocytes and T lymphocytes and plays a role in the differentiation of memory NK cells. Here we established that mouse cytomegalovirus (MCMV) downregulates the surface expression of PVR and we also characterized the viral protein that retains PVR intracellulary, in spite of an increased transcriptional activity of PVR locus. Since PVR can ligate both inhibitory and activating receptors, the real consequence of PVR downregulation for the immune response is hard to predict. However, MCMV lacking PVR inhibitor was dramatically attenuated in vivo and this attenuated phenotype was only in part due to an augmented virus control by NK cells, while the depletion of macrophages completely abolishes this attenuation. A strong effect of NK cells and macrophages was correlated with a dominant expression of DNAM-1 on these cells upon in vivo infection, while the level of TIGIT receptor was significantly lower. Altogether, our results reveal that DNAM-1 has a physiological significance in virus control by NK cells and macrophages during the early days post infection.

CD155; DNAM1; TIGIT

nije evidentirano