Tolerance to virus infection in PLoS Pathogens

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In a recent PLoS pathogens paper, Sarah Merkling and Gijs Overheul in the group of Dr. Ronald van Rij (Dept. Medical Microbiology), in collaboration with Dr. Jamie Kramer and Dr. Annette Schenck (dept. Human Genetics) elucidated a novel epigenetics-based mechanism for tolerance.

Multicellular organisms use two defense strategies to fight microbial infections: resistance and tolerance (also termed resilience). Resistance involves the detection and eradication of the invading pathogen by the immune system (resistance). Tolerance mechanisms reduce the negative effects of microbial infection on host fitness, for example, by reducing damage inflicted by the pathogen or by limiting the adverse effects of the immune response. While resistance mechanisms have classically received much attention, little is known about the mechanism of tolerance.

Using the fruit fly Drosophila as a model, Merkling and colleagues now identify the epigenetic regulator G9a (also known as EHMT) as an important mediator of tolerance. The authors found that G9a-deficient flies were hypersensitive to RNA virus infection. Exploiting the genetic toolbox in Drosophila, it was shown that G9a dampens the evolutionary conserved Jak-Stat pathway to prevent immunopathology. The authors propose epigenetic regulation of immunity as a new mechanism for disease tolerance.

Reference: Merkling SM, Bronkhorst AM, Kramer JM, Overheul GJ, Schenck A, Van Rij RP, The Epigenetic Regulator G9a Mediates Tolerance to RNA Virus Infection in Drosophila. PLoS Pathogens 11: e1004692 

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