engleski

The role of viral immunoevasins in the pathogenesis of cytomegalovirus infection

Natural killer (NK) cells provide protection from murine cytomegalovirus (MCMV) in the early days of the infection. The recognition of target cells by NK cells is regulated by the balance of signaling by inhibitory and stimulatory receptors specific for cell surface ligands. NKG2D is a stimulatory receptor on NK cells that has been implicated in the recognition of cells infected with viruses. Cell surface ligands for NKG2D in mouse include the RAE-1, MULT-1 and H60 proteins. We have recently identified three MCMV proteins which belong to the large set of MCMV genes, the m145 gene family, and selectively target NKG2D ligands for attenuating NK response during infection. The product of the m145 gene acts as a selective inhibitor of MULT-1, a prime ligand of the activating NKG2D receptor in mouse. The m152-encoded glycoprotein was demonstrated to block surface expression of RAE-1-family members and the NKG2D ligand H60 is down-regulated by m155. Now we have evidence that MCMV possesses additional gene(s) involved in the inhibition of NK cell activation via NKG2D. We have shown previously that the effect of m145 as well as m155 on MULT-1 and H60, respectively, must take place in a compartment beyond ERGIC/cis-Golgi. Furthermore our present results indicated that the surface portion of MULT-1 is down-regulated via clathrin-dependent endocytosis and degraded in lysosomes. Altogether, the identification of these viral imunoevasive functions and the corresponding cellular pathways that are involved in them are likely to contribute to better understanding the pathogenesis of herpesviral infections.

cytomegalovirus; NK cells; NKG2D; immune evasion

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