The Epigenetic Regulator G9a Mediates Tolerance to RNA Virus Infection in Drosophila

PLoS Pathogens

Jamie M. Kramer¹  Annette Schenck¹  Alfred W. Bronkhorst²  Ronald P. Van Rij²  Sarah H. Merkling²  Gijs J. Overheul² 

[1] Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands;Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands

关键词: JAK-STAT signaling cascade;    Fats;    Gene expression;    Drosophila melanogaster;    Immune response;    RNA viruses;    RNA interference;    Viral gene expression;   

DOI  :  10.1371/journal.ppat.1004692

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY