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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Chromatin Immunoprecipitation
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Drosophila melanogaster / enzymology
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Drosophila melanogaster / immunology
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Drosophila melanogaster / virology*
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Epigenesis, Genetic*
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Gene Expression Regulation / immunology*
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Histone-Lysine N-Methyltransferase / immunology*
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Immune Tolerance / immunology*
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RNA Virus Infections / immunology*
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RNA Viruses
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Reverse Transcriptase Polymerase Chain Reaction
Substances
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Histone-Lysine N-Methyltransferase
Grants and funding
This work is supported by a PhD fellowship from Radboud Institute for Molecular Life Sciences (
http://www.rimls.nl) to SHM, VIDI fellowships from the Netherlands Organization for Scientific Research to AS and RPVR (project numbers 917.96.346 and 864.08.003;
http://www.nwo.nl), a European Union FP7 large scale integrated network grant to AS (Gencodys, HEALTH-241995;
http://www.gencodys.eu) and a Horizon Breakthrough fellowship from the Netherlands Genomics Initiative to RPVR (project number 93511004;
http://www.genomics.nl). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.