title: The epigenetic regulator G9a mediates tolerance to RNA virus infection in Drosophila.
abstract: Little is known about the tolerance mechanisms that reduce the negative effects of microbial infection on host fitness. Here, we demonstrate that the histone H3 lysine 9 methyltransferase G9a regulates tolerance to virus infection by shaping the response of the evolutionary conserved Jak-Stat pathway in Drosophila. G9a-deficient mutants are more sensitive to RNA virus infection and succumb faster to infection than wild-type controls, which was associated with strongly increased Jak-Stat dependent responses, but not with major differences in viral load. Genetic experiments indicate that hyperactivated Jak-Stat responses are associated with early lethality in virus-infected flies. Our results identify an essential epigenetic mechanism underlying tolerance to virus infection.
authors.affiliation: Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Merkling
authors.affiliation: Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Alfred W
authors.initials: AW
authors.lastname: Bronkhorst
authors.affiliation: Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jamie M
authors.initials: JM
authors.lastname: Kramer
authors.affiliation: Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Gijs J
authors.initials: GJ
authors.lastname: Overheul
authors.affiliation: Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Annette
authors.initials: A
authors.lastname: Schenck
authors.affiliation: Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Van Rij
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D004331:Drosophila melanogaster / Q000201:enzymology / Q000276:immunology / Q000821:virology*; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation / Q000276:immunology*; D011495:Histone-Lysine N-Methyltransferase / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D012327:RNA Virus Infections / Q000276:immunology*; D012328:RNA Viruses; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D011495:Histone-Lysine N-Methyltransferase