Naslov
Murine cytomegalovirus perturbs endosomal trafficking of MHC class I molecules in the early phase of infection

Autori
Ilić Tomaš, Maja ; Kučić, Natalia ; Mahmutefendić, Hana ; Blagojević, Gordana ; Lučin, Pero

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

Izvornik
Book of Abstracts of the 10th Congress of the Croatian Society of Biochemistry and Molecular Biology / The secret life of biomolecules / Zrinka Kovarik, Jadranka Varljen (ur.). - Rijeka : Hrvatsko Društvo za Biotehnologiju, 2010, 111-111

Skup
10th Congress of the Croatian Society of Biochemistry and Molecular Biology with international participation

Mjesto i datum
Opatija, Hrvatska, 15.09.2010. - 18.09.2010

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
Murine cytomegalovirus; immunoevasins; endosomal trafficking; MHC class I molecules

Sažetak
Murine cytomegalovirus (MCMV) perturbs endosomal trafficking very early in the infection. This perturbation has striking impact on endosomal trafficking of Major Histocompatibility Class I (MHC-I) molecules due to the effect of MCMV immunoevasins that act in the secretory pathway at the same time. 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 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. In infected cells, constitutively endocytosed MHC-I complexes retained in EEA1-positive and LBPA-negative perinuclear endosomes together with clathrin-dependent cargo (transferrin receptor, Lamp1 and EGFR). From these endosomes MHC-I complexes slowly progress into the recycling route and into the degradative route. MCMV arrests endocytic trafficking in sorting endosomes at the stage prior to partitioning of recycling and endolysosomal domains. This arrest was associated with the reduction of intracellular content of Rab7 and Rab11 – small GTPases. Reduced recycling of MHC-I, when combined with reduced egress of newly synthesized MHC-I from the secretory pathway achieved by the immunoevasins, results in the complete loss of MHC-I from the cell surface. The striking effect of MCMV on MHC-I cell surface level in the early phase of infection discovers a mechanism of endosomal remodeling very early in the infection. Understanding the mechanism of formation of the perinuclear endosomal retention compartment may contribute to the understanding molecular and mechanistic events in endosomal maturation and formation of the recycling endosomes and LE.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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