Naslov
Multiple Strategies to Evade NKG2D by MCMV

Autori
Jonjić, Stipan

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Innate Immunity to Pathogens / Yokoyama, W.M. ; Biron, C.A. ; Kaufmann, S.H.E. - Steamboat Springs (CO) : Keystone Symposia, 2005, 36-36

Skup
Innate Immunity to pAthogens

Mjesto i datum
Steamboat Springs (CO), Sjedinjene Američke Države, 08.01.2005. - 13.01.2005

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
MCMV. NKG2D; immunoevasion

Sažetak
Based on their early susceptibility to MCMV infection, mouse strains are either susceptible (e.g. BALB/c mice) or resistant (e.g. C57BL/6 mice) to this virus. MCMV titers in the psleen of mice inversely correlate with their ability to exhibit an effective NK cell response, which is controlled by the alleles of the Cmv1 locus conferring either susceptibility (Cmv1s) or resistance (Cmv1r). However, the inability of Cmv1s mice to generate an effective NK cell response to MCMV is not their constitutive characteristic since their NK cells can protect against other viruses. We have previously shown that Cmv1s mice can exert sufficient NK cell response to MCMV but this function is prevented by viral proteins that down-modulate the cellular ligands for activating NK cell receptor NKG2D. Up to now three ligands for the NKG2D receptor have been identified in mice: RAE-1, H60 nad MULT-1. The MCMV m152/gp40 has a double role as it modulates not only the plasma membrane expression of MHC class I molecules, but also of NKG2D ligands RAE-1. To escape NK cell control it is not sufficient that the virus down-regulates only one of the three different NKG2D ligands, since the remaining ligand might be sufficient to trigger NK cell activation. Therefore, we postulated that in addition to m152/gp40, there should be other MCMV proteins involved in the control of the expression of NKG2D ligands other than RAE-1. We have found that the proteins encoded by m145 and m155 genes are responsible for the down-regulation of MULT-1 and H60, respectively. Since deletion of the m155 gene only partially restores the expression of H60, we concluded that there must be an additional, so far unknown, MCMV function involved in the regulation of H60. While MCMV does not up-regulate the expression of H60, it strongly induces MULT-1 expression inspite of its surface down-modulation. The importance of MULT-1 and H60 in NK cell regulation in vivo was confirmed by the attenuating effect of the m145 or m155 gene deletion, which could be lifted after NK cell depletion. Our findings underline the significance of escaping NKG2D signaling for viral survival and maintenance. Potential mechanisms by which m145 and m155 interfere with thier cellular targets will also be discussed.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA