The Epigenetic Regulator G9a Mediates Tolerance to RNA Virus Infection in

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Multicellular organisms deploy various strategies to fight microbial infections. Invading pathogens may be eradicated directly by antimicrobial effectors of the immune system. Another strategy consists of increasing the tolerance of the host to infection, for example, by limiting the adverse effects of the immune response. The molecular mechanisms underlying this novel concept remain largely uncharacterized. Here, we demonstrate that the epigenetic regulator G9a mediates tolerance to virus infection in Drosophila. We found that G9a-deficient flies succumb faster than control flies to infection with RNA viruses, but that the viral burden did not significantly differ. Unexpectedly, mutant flies express higher levels of genes that are regulated by the Jak-Stat signaling pathway, which in other studies was found to be important for antiviral defense. Exploiting the genetic toolbox in Drosophila, we demonstrate that Jak-Stat hyperactivation induces early mortality after virus infection. Precise control of immune pathways is essential to ensure efficient immunity, while preventing damage due to excessive immune responses. Our results indicate that G9a, an epigenetic modifier, dampens Jak-Stat responses to prevent immunopathology. Therefore, we propose epigenetic regulation of immunity as a new paradigm for disease tolerance.

Vyšlo v časopise: The Epigenetic Regulator G9a Mediates Tolerance to RNA Virus Infection in. PLoS Pathog 11(4): e32767. doi:10.1371/journal.ppat.1004692
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004692

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