The epigenetic regulator G9a mediates tolerance to RNA virus infection in Drosophila

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 pathwa...

Full description

Saved in:
Bibliographic Details
Published in:PLoS pathogens 2015-04, Vol.11 (4), p.e1004692-e1004692
Main Authors: Merkling, Sarah H, Bronkhorst, Alfred W, Kramer, Jamie M, Overheul, Gijs J, Schenck, Annette, Van Rij, Ronald P
Format: Article
Language:English
Subjects:
Animals
Chromatin Immunoprecipitation
Colleges & universities
Datasets
Drosophila
Drosophila melanogaster - enzymology
Drosophila melanogaster - immunology
Drosophila melanogaster - virology
Epigenesis, Genetic
Epigenetic inheritance
Epigenetics
Experiments
Gene expression
Gene Expression Regulation - immunology
Genetic aspects
Health aspects
Histone-Lysine N-Methyltransferase - immunology
Host-virus relationships
Identification and classification
Immune system
Immune Tolerance - immunology
Infections
Insects
Kinases
Life Sciences
Mortality
Reverse Transcriptase Polymerase Chain Reaction
RNA virus infections
RNA Virus Infections - immunology
RNA Viruses
Scholarships & fellowships
Transcription factors
Viruses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1004692