The poxviral scrapin MV-LAP requires a myxoma viral infection context to efficiently downregulate MHC-I molecules.
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.
Collin
Nicolas
N
UMR 1225 Interactions Hôtes Agents pathogènes, INRA/ENVT, Ecole Nationale Vétérinaire de Toulouse, 23 chemin des Capelles, BP87614, 31076 Toulouse cedex 03, France.
Guérin
Jean-Luc
JL
Drexler
Ingo
I
Blanié
Sophie
S
Gelfi
Jacqueline
J
Boullier
Séverine
S
Foucras
Gilles
G
Sutter
Gerd
G
Messud-Petit
Frédérique
F
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017124:Conserved Sequence; D004279:DNA, Viral / Q000235:genetics; D015536:Down-Regulation; D005814:Genes, Viral; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D009233:Myxoma virus / Q000235:genetics / Q000502:physiology*; D009234:Myxomatosis, Infectious / Q000235:genetics / Q000276:immunology; D010449:Peptide Mapping; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D004279:DNA, Viral; D015395:Histocompatibility Antigens Class I; C450447:MV-LAP protein, Myoxoma; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins