Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35401, USA.
Present Address: Indiana University School of Medicine-Indianapolis, Medical Scientist Training Program, Indianapolis, IN 46202, USA.
Aging (Albany NY). 2023 Mar 22;15(6):1748-1767. doi: 10.18632/aging.204593.
Aging is accompanied by increased susceptibility to infections including with viral pathogens resulting in higher morbidity and mortality among the elderly. Significant changes in host metabolism can take place following virus infection. Efficient immune responses are energetically costly, and viruses divert host molecular resources to promote their own replication. Virus-induced metabolic reprogramming could impact infection outcomes, however, how this is affected by aging and impacts organismal survival remains poorly understood. RNA virus infection of with Flock House virus (FHV) is an effective model to study antiviral responses with age, where older flies die faster than younger flies due to impaired disease tolerance. Using this aged host-virus model, we conducted longitudinal, single-fly respirometry studies to determine if metabolism impacts infection outcomes. Analysis using linear mixed models on Oxygen Consumption Rate (OCR) following the first 72-hours post-infection showed that FHV modulates respiration, but age has no significant effect on OCR. However, the longitudinal assessment revealed that OCR in young flies progressively and significantly decreases, while OCR in aged flies remains constant throughout the three days of the experiment. Furthermore, we found that the OCR signature at 24-hours varied in response to both experimental treatment and survival status. FHV-injected flies that died prior to 48- or 72-hours measurements had a lower OCR compared to survivors at 48-hours. Our findings suggest the host's metabolic profile could influence the outcome of viral infections.
衰老伴随着对感染的易感性增加，包括病毒病原体感染，导致老年人发病率和死亡率更高。病毒感染后，宿主代谢会发生显著变化。有效的免疫反应需要消耗大量能量，而病毒会转移宿主的分子资源来促进自身复制。病毒诱导的代谢重编程可能会影响感染结果，但是，衰老如何影响这一点以及对生物体存活的影响仍知之甚少。使用 Flock House 病毒（FHV）感染 是研究随年龄变化的抗病毒反应的有效模型，在该模型中，由于疾病耐受性受损，年老的苍蝇比年轻的苍蝇死亡得更快。利用这种老化的宿主-病毒模型，我们进行了纵向、单蝇呼吸测量研究，以确定代谢是否会影响感染结果。对感染后最初 72 小时内的耗氧量（OCR）进行线性混合模型分析表明，FHV 可调节呼吸，但年龄对 OCR 没有显著影响。然而，纵向评估显示，年轻苍蝇的 OCR 逐渐显著下降，而老年苍蝇的 OCR 在整个三天的实验过程中保持不变。此外，我们发现，24 小时的 OCR 特征对实验处理和存活状态都有响应。在 48 小时或 72 小时测量之前死亡的感染了 FHV 的苍蝇的 OCR 低于 48 小时的幸存者。我们的研究结果表明，宿主的代谢特征可能会影响病毒感染的结果。
