Naslov
Modulation of NK cell response by mouse cytomegaloviru.
(Modulation of NK cell response by mouse cytomegalovirus.)

Autori
Krmpotić, Astrid ; Lenac, Tihana ; Hasan, Milena ; Arapović, Jurica ; Jonjić, Stipan

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, pp prezentacija, znanstveni

Skup
EMBO/HHMI Central European Scientists Meeting

Mjesto i datum
Cavtat, Hrvatska, 15.06.2006. - 17.06.2006

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
cytomegalovirus; NK cells; immune evasion

Sažetak
NK cells have the imperative role in the early control of cytomegalovirus (CMV) infection. The infection of mice with mouse CMV (MCMV) is used as a model for studying the role of NK cells during CMV infection. An evolutionary struggle between NK cells and CMV can be inferred from the existence of a broad range of viral mechanisms designed to compromise NK cell function. NK cell response is regulated by the balance of signaling by inhibitory and activating receptors specific for cell surface ligands. NKG2D is an activating receptor on NK cells that has been implicated in the recognition of cells infected with viruses. In mice, RAE-1 family of proteins, H60 and MULT-1 were identified as ligands for NKG2D receptor. These ligands are poorly expressed on the surface of most normal cells but are transcriptionally upregulated in infected cells. We have recently identified three MCMV proteins that selectively target NKG2D ligands. The product of m145 gene acts as a selective inhibitor of MULT-1 whereas the m152-encoded glycoprotein was demonstrated to block the surface expression of RAE-1-family members. The NKG2D ligand H60 is down-regulated by the product of m155 gene. We have recently discovered another viral immunoevasin that prevents NK cell activation via NKG2D. MCMV fcr-1/m138 protein that specifically binds to the Fc part of IgG is also able to down-regulate NKG2D ligands MULT-1 and H60. The importance of these viral proteins in the evasion of NK cells was confirmed also in vivo. We are currently attempting to identify mechanisms by which these viral proteins regulate the expression of NKG2D ligands. Altogether, the identification of viral immunoevasins and the mechanisms of their interference with immune receptors and their ligands are likely to contribute to better understanding of the pathogenesis of CMV infections.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA