engleski

Murine cytomegalovirus arrests cell surface MHC class I molecules in the pre-late endosomal compartment during early stage of infection

Murine cytomegalovirus (MCMV) downregulates MHC class I molecules (MHC-I) from the cell surface at early stage of infection (6 hrs.p.i.). The aim of our study was to to identify the compartment wherein virus transposes these molecules from the cell surface. Mouse embrional fibroblasts (MEFs) were infected with wild type and deletion mutant of MCMV devoid of viral Fc receptor gene. Intracellular localization and trafficking of MHC-I molecules was determined by confocal microscopy. Cell surface expression of MHC-I molecules was followed by flow-cytometry and intracellular stability by immunoprecipitation after cell surface biotynilation. MHC-I were labeled with monoclonal antibody MA-215 (Kd) and 34-5-8s (Dd). In order to define a compartment wherein MHC-I are arrested we colocalised them with a various palettes of endosomal markers. Trafficking of Ab-labeled cell surface MHC-I was compared with well known internalization pathway of TfR (Ab R-17). Cell surface Kd and Dd molecules are down-regulated in infected cells. Following the internalization, these molecules are arrested in pre-late compartment as large vesiculo-tubular structures. Passing through the endocytic compartments Kd and Dd molecules are completely colocalised with EEA-1, partially with GM130 and neither with LBPA nor LAMP-1. During the whole mutual internalization (6-13 hrs p.i.), MHC-I and TfR they are completely colocalised indicating that MHC-I followed the same endocytic route as TfR. Virus down-regulates the MHC-I from the cell surface of infected cells, sorting them through the different endosomal structures and arrested them into pre-late compartment.

murine cytomegalovirus; cell surface MHC class I molecules; endosomes

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