Age-dependent impairment of disease tolerance is associated with a robust transcriptional response following RNA virus infection in Drosophila

Abstract

Advanced age in humans is associated with greater susceptibility to and higher mortality rates from infections, including infections with some RNA viruses. The underlying innate immune mechanisms, which represent the first line of defense against pathogens, remain incompletely understood. Drosophila melanogaster is able to mount potent and evolutionarily conserved innate immune defenses against a variety of microorganisms including viruses and serves as an excellent model organism for studying host-pathogen interactions. With its relatively short lifespan, Drosophila also is an organism of choice for aging studies. Despite numerous advantages that this model offers, Drosophila has not been used to its full potential to investigate the response of the aged host to viral infection. Here, we show that, in comparison to younger flies, aged Drosophila succumb more rapidly to infection with the RNA-containing Flock House virus due to an age-dependent defect in disease tolerance. Relative to younger individuals, we find that older Drosophila mount transcriptional responses characterized by differential regulation of more genes and genes regulated to a greater extent. We show that loss of disease tolerance to Flock House virus with age associates with a stronger regulation of genes involved in apoptosis, some genes of the Drosophila immune deficiency NF-kappa B pathway, and genes whose products function in mitochondria and mitochondrial respiration. Our work shows that Drosophila can serve as a model to investigate host-virus interactions during aging and furthermore sets the stage for future analysis of the age-dependent mechanisms that govern survival and control of virus infections at older age.

Description
Keywords
aging, infection, disease tolerance, RNA virus, Drosophila melanogaster, transcriptomics, INNATE IMMUNE-RESPONSE, LONG NONCODING RNAS, FLOCK HOUSE VIRUS, ANTIVIRAL IMMUNITY, FUNCTIONAL-ANALYSIS, HOST-DEFENSE, COLEOPTERA, APOPTOSIS, PROFILES, DECLINES, Genetics & Heredity
Citation
Sheffield, L., Sciambra, N., Evans, A., Hagedorn, E., Goltz, C., Delfeld, M., Kuhns, H., Fierst, J. L., & Chtarbanova, S. (2021). Age-dependent impairment of disease tolerance is associated with a robust transcriptional response following RNA virus infection in Drosophila. In J. Tennessen (Ed.), G3 Genes|Genomes|Genetics (Vol. 11, Issue 7). Oxford University Press (OUP). https://doi.org/10.1093/g3journal/jkab116