Transcriptional response of aged Drosophila melanogaster following infection with an RNA virus

Presentation of poster 1962C at TAGC 2020 Online.

We investigated how aging impacts Drosophila’s ability to respond to FHV infection. We demonstrate that wild type 30-days-old Drosophila succumb more rapidly to infection in comparison with younger (5-days-old) adults and that the increased mortality is not accompanied by an increase in virus load. These results suggest that mechanisms different from those in control of pathogen burden affect survival to FHV infection of the aged organism. We next used RNA sequencing (RNAseq) to compare transcriptional responses of young and aged Drosophila hosts that have been infected with FHV or injected with a control solution. We found that two days post-infection, older hosts exhibited larger transcriptional responses than younger individuals, upregulating ~2 times more genes and downregulating ~2.8 times more genes than young flies. Among differentially regulated genes for both age groups, we found 93% and 57% overlap between upregulated and downregulated genes, respectively. Gene ontology analysis for Biological processes of differentially regulated genes in older FHV-infected flies revealed strongest upregulation of genes encoding for factors involved in neurogenesis and transcription and strongest downregulation for genes involved in organismal reproduction and proteolysis as well as carbohydrate and lipid metabolism. Among genes specifically downregulated in aged FHV-infected flies, we found an enrichment for mitochondria-related genes. This suggests that FHV infection possibly promotes deregulation of metabolic function in the aged fly leading to more rapid death.

Our findings will set the stage for future analysis of the mechanisms that underlie the increased mortality of older flies and the identification of novel age-specific factors associated with this process.