Murine cytomegalovirus perturbs endosomal trafficking of major histocompatibility complex class I molecules in the early phase of infection.
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.
Tomas
Maja Ilić
MI
Department of Physiology and Immunology, University of Rijeka School of Medicine, Braće Branchetta 20, 51000 Rijeka, Croatia.
Kucić
Natalia
N
Mahmutefendić
Hana
H
Blagojević
Gordana
G
Lucin
Pero
P
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
D015395:Histocompatibility Antigens Class I; D019707:Receptors, Chemokine