Naslov
Expression of the Human Cytomegalovirus UL11 Glycoprotein in Viral Infection and Evaluation of its Effect on Virus-Specific CD8 T Cells

Autori
Gabaev, I. ; Elbasani, E. ; Ameres, S. ; Steinbrück, L. ; Stanton, R. ; Döring, M. ; Lenac Roviš, Tihana ; Kalinke, U. ; Jonjić, Stipan ; Moosmann, A. ; Messerle, M.

Izvornik
Journal of virology (0022-538X) 88 (2014), 24; 14326-14339

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
HCMV; Human Cytomegalovirus; UL11; CD45

Sažetak
The human cytomegalovirus (CMV) UL11 open reading frame (ORF) encodes a putative type I transmembrane glycoprotein, which displays remarkable amino acid sequence variability among different CMV isolates, suggesting that it represents an important virulence factor. In a previous study we have shown that UL11 can interact with the cellular receptor tyrosine phosphatase CD45, which has a central role for signal transduction in T cells, and treatment of T cells with high amounts of a soluble UL11 protein inhibited their proliferation. In order to analyze UL11 expression in CMV-infected cells, we constructed CMV recombinants that either encode tagged UL11 versions or carry a stop mutation in the UL11 ORF. Moreover, we examined whether UL11 affects the function of virus-specific cytotoxic T lymphocytes (CTL). We found that the UL11 ORF gives rise to several proteins due to both posttranslational modification and alternative translation initiation sites. Biotin labelling of surface proteins on infected cells indicated that only highly glycosylated UL11 forms are present at the plasma membrane, whereas low glycosylated UL11 forms were found in the endoplasmic reticulum. We did not find evidence of UL11 cleavage and secretion of a soluble UL11 version. Co-cultivation of CTLs recognizing different CMV epitopes with fibroblasts infected with a UL11 deletion mutant or the parental strain revealed that under the conditions applied UL11 did not influence the activation of CMV-specific CD8 T cells. For further studies we propose to investigate the interaction of UL11 with CD45 and the functional consequences in other immune cells expressing CD45.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA