title: Murine cytomegalovirus perturbs endosomal trafficking of major histocompatibility complex class I molecules in the early phase of infection.
abstract: Murine cytomegalovirus (MCMV) functions interfere with protein trafficking in the secretory pathway. In this report we used Δm138-MCMV, a recombinant virus with a deleted viral Fc receptor, to demonstrate that MCMV also perturbs endosomal trafficking in the early phase of infection. This perturbation had a striking impact on cell surface-resident major histocompatibility complex class I (MHC-I) molecules due to the complementary effect of MCMV immunoevasins, which block their egress from the secretory pathway. In infected cells, constitutively endocytosed cell surface-resident MHC-I molecules were arrested and retained in early endosomal antigen 1 (EEA1)-positive and lysobisphosphatidic acid (LBPA)-negative perinuclear endosomes together with clathrin-dependent cargo (transferrin receptor, Lamp1, and epidermal growth factor receptor). Their progression from these endosomes into recycling and degradative routes was inhibited. This arrest was associated with a reduction of the intracellular content of Rab7 and Rab11, small GTPases that are essential for the maturation of recycling and endolysosomal domains of early endosomes. The reduced recycling of MHC-I in Δm138-MCMV-infected cells was accompanied by their accelerated loss from the cell surface. The MCMV function that affects cell surface-resident MHC-I was activated in later stages of the early phase of viral replication, after the expression of known immunoevasins. MCMV without the three immunoevasins (the m04, m06, and m152 proteins) encoded a function that affects endosomal trafficking. This function, however, was not sufficient to reduce the cell surface expression of MHC-I in the absence of the transport block in the secretory pathway.
authors: Department of Physiology and Immunology, University of Rijeka School of Medicine, Braće Branchetta 20, 51000 Rijeka, Croatia.
authors: Maja Ilić
authors: MI
authors: Tomas
authors: Natalia
authors: N
authors: Kucić
authors: Hana
authors: H
authors: Mahmutefendić
authors: Gordana
authors: G
authors: Blagojević
authors: Pero
authors: P
authors: Lucin
mesh_terms: D000818:Animals; D011992:Endosomes / Q000378:metabolism*; D006566:Herpesviridae Infections; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D051379:Mice; D018146:Muromegalovirus / Q000502:physiology*; D009154:Mutation; D021381:Protein Transport; D019707:Receptors, Chemokine; D013997:Time Factors; D014779:Virus Replication
chemical_list: D015395:Histocompatibility Antigens Class I; D019707:Receptors, Chemokine