engleski

Two MCMV regulators of PVR

The recognition of CMV infected cells by NK cells is regulated by the balance of signals via inhibitory and stimulatory receptors specific for cell surface ligands which are either of host or viral origin. Human CD155 (polio virus receptor, PVR), which is expressed by numerous tumors and healthy cells, is recognized by three different receptors: two co-stimulating receptors (CD96 and DNAM1) and one inhibitory receptor (TIGIT). All three receptors seem to be expressed by all NK cells. A large number of cytomegalovirus (CMV) genes modulate the innate and adaptive host immune response, most likely to the advantage of the pathogen. The downregulation of human PVR by UL141 product of human CMV has been demonstrated previously. Here we show that mouse PVR is regulated by murine CMV (MCMV) causing its partial downregulation from the surface of infected cells. We have evidence that at least two MCMV gene products are involved in the downregulation of PVR. One of these is the m154 gene product whose effect was also confirmed in vivo, since MCMV mutant lacking m154 gene is attenuated 3 days post infection. The second regulator is an MCMV gene from the region m18-m22. This so far undefined inhibitor causes PVR retention in the endoplasmic reticulum (ER). Since TIGIT binds PVR with high affinity as compared to DNAM1 and CD96, we suggest that the partial downregulation of PVR facilitates the escape from DNAM1 and CD96, while still enabling inhibition by TIGIT.

MCMV regulators; PVR; TIGIT

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