Article: article from journal or magazin.
The poxviral scrapin MV-LAP requires a myxoma viral infection context to efficiently downregulate MHC-I molecules.
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Downregulation of MHC class I molecules is a strategy developed by some viruses to escape cellular immune responses. Myxoma virus (MV), a poxvirus causing rabbit myxomatosis, encodes MV-LAP that is known to increase MHC-I endocytosis and degradation through a C(4)HC(3) motif critical for an E3 ubiquitin ligase activity. Here, we performed a functional mapping of MV-LAP and showed that not only the C(4)HC(3) motif is necessary for a marked downregulation of MHC-I but also a conserved region in the C-terminal part of the protein. We also showed that the putative transmembrane domains are responsible for a specific subcellular localization of the protein: they retain MV-LAP in the ER in transfected cells and in the endolysosomal compartments in infected cells. We observed that a specific MV infection context is necessary for a fully efficient downregulation of MHC-I. Our data suggest that the functionality of viral LAP factors, inherited by herpes- and poxviruses from mammalian cells, is more complex than anticipated.
Amino Acid Sequence, Animals, Base Sequence, Cell Line, Conserved Sequence, DNA, Viral/genetics, Down-Regulation, Genes, Viral, Histocompatibility Antigens Class I/metabolism, Membrane Proteins/chemistry, Membrane Proteins/genetics, Molecular Sequence Data, Mutation, Myxoma virus/genetics, Myxoma virus/physiology, Myxomatosis, Infectious/genetics, Myxomatosis, Infectious/immunology, Peptide Mapping, Rabbits, Recombinant Fusion Proteins/chemistry, Recombinant Fusion Proteins/genetics, Sequence Homology, Amino Acid, Transfection, Viral Proteins/chemistry, Viral Proteins/genetics
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