Naslov
REGULATION OF THE EXPRESSION OF NKG2D LIGANDS MULT-1 AND H60 BY MCMV

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

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

Izvornik
Annual Meeting of the Croatian Immunological Society 2005 / - Rijeka, 2005

Skup
Annual Meeting of the Croatian Immunological Society 2005

Mjesto i datum
Božava, Hrvatska, 29.09.2005. - 02.10.2005

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
cytomegalovirus; H60; m145; m155; MULT-1; NK cell; NKG2D receptor

Sažetak
NK cells have imperative role in the early control of cytomegalovirus (CMV) infection. Both human and mouse CMV encode proteins that inhibit the activation of NK cells by down-regulating the cellular ligands for the activating NK cell receptor, NKG2D. MCMV proteins m145, m152 and m155 interfere with the expression of all three known NKG2D ligands, MULT-1 (Krmpotic A. et al, J Exp Med, 201 (2): 211-220, 2005), Rae-1 (Krmpotic A. et al, Nat Immunol, 3 (6): 529-535, 2002, Lodoen M. et al, J Exp Med, 197 (10): 1245-1253, 2003) and H60 (Hasan M. et al, J Virol, 79 (5): 2920-2930, 2005), respectively. The importance of these viral genes in evasion of NK cells was confirmed also in vivo. In an attempt to identify potential mechanisms by which m145 and m155 interfere with their cellular targets, we have performed RT PCR studies and revealed that there is no block on the transcriptional level. Immunoprecipitation experiments confirmed that the m145- as well as m155-mediated effect must take place in a compartment beyond ERGIC/cis-Golgi. We showed the colocalization of MULT-1 and H60 with TGN and endo-lysosomal compartment in infected and uninfected cells. Next we examined whether the MULT-1 is blocked on its transport to the cell surface or down-regulated from the plasma membrane. We found out that the surface portion of MULT-1 is down-regulated via clathrin dependent endocytosis and degraded in lysosomes. Unexpectedly, in addition to m145 gene product we uncovered that another viral protein is needed to accomplish this function.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA