Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, USA.
G3 (Bethesda). 2021 Jul 14;11(7). doi: 10.1093/g3journal/jkab116.
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-kB 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.
人类的高龄与感染的易感性增加和死亡率升高有关，包括某些 RNA 病毒的感染。先天免疫机制是抵御病原体的第一道防线，但仍不完全清楚。黑腹果蝇能够对包括病毒在内的多种微生物产生强大且进化保守的先天免疫防御，是研究宿主-病原体相互作用的理想模型生物。由于其相对较短的寿命，果蝇也是衰老研究的首选生物体。尽管这种模型具有许多优势，但尚未充分利用果蝇来研究衰老宿主对病毒感染的反应。在这里，我们表明，与年轻的果蝇相比，年老的果蝇由于对疾病耐受性的年龄依赖性缺陷，更容易受到含有 RNA 的 Flock House 病毒的感染。与年轻个体相比，我们发现较老的果蝇会产生转录反应，其特征是更多基因的差异调节以及更大程度的基因调节。我们表明，随着年龄的增长，对 Flock House 病毒的疾病耐受性丧失与凋亡相关基因、果蝇免疫缺陷 NF-kB 途径的一些基因以及其产物在线粒体和线粒体呼吸中发挥作用的基因的更强调节有关。我们的工作表明，果蝇可以作为研究衰老过程中宿主-病毒相互作用的模型，并且为未来分析衰老相关机制奠定了基础，这些机制决定了老年时的生存和病毒感染的控制。
