In humans, many aspects of the interferon-induced anti-viral response are mediated by the JAK-STAT signaling pathway. Experiments in Drosophila characterizing tolerance to RNA virus infection have led to the identification of an epigenetic mechanism, involving the Drosophila histone H3 lysine 9 methyltransferase G9a, that modulates the viral-infection-induced response of the JAK-STAT signaling pathway. There are two genes orthologous to Dmel\G9a in human, EHMT1 and EHMT2. Classical loss-of-function mutations, RNAi targeting constructs, alleles caused by insertional mutagenesis, and an amorphic allele created by targeted recombination have been generated for Dmel\G9a. The human EHMT1 is implicated in Kleefstra syndrome (MIM:610253; FBhh0000556).
Neither human gene has been introduced into flies.
Animals homozygous for an amorphic mutation of Dmel\G9a survive to adulthood and are fertile, however, they are more sensitive to RNA virus infection; reduced adult lifespan is observed for G9a-deficient virus-infected flies. Multiple viruses were tested (introduced by intra-thoracic injection); increased susceptibility was observed for all RNA viruses tested, but not for the single DNA virus tested. Physical and genetic interactions of G9a have been described; see below and in the G9a gene report.
[updated Sep. 2017 by FlyBase; FBrf0222196]
The interferon (IFN) induced anti-viral response is among the earliest and most potent of the innate responses to fight viral infection. The induction of the Janus kinase/signal transducer and activation of transcription (JAK/STAT) signalling pathway by IFNs leads to the upregulation of hundreds of interferon-stimulated genes (ISGs) (Fleming, 2016; pubmed:27367734).
Results in Drosophila identify an epigenetic mechanism underlying tolerance to virus infection. The Drosophila histone H3 lysine 9 methyltransferase G9a regulates tolerance to virus infection by modulating the response of the JAK-STAT signaling pathway. G9a-deficient mutants are more sensitive to RNA virus infection; early lethality is observed in G9a-deficient virus-infected flies.
Many to one: 2 human to 1 Drosophila; the human genes are EHMT1 and EHMT2.
Many to one: 2 human to 1 Drosophila; the human genes are EHMT1 and EHMT2.
Moderate-scoring ortholog of human EHMT2 and EHMT1 (1 Drosophila to 2 human); there are lower-scoring orthologs in both species. Dmel\G9a shares 26-28% identity and 41-42% similarity with the human genes.
