Research Paper Volume 15, Issue 6 pp 1748—1767
RNA virus-mediated changes in organismal oxygen consumption rate in young and old Drosophila melanogaster males
- 1 Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35401, USA
- 2 Present Address: Indiana University School of Medicine-Indianapolis, Medical Scientist Training Program, Indianapolis, IN 46202, USA
- 3 Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Biostatistics Consulting Center, Bloomington, IN 47405, USA
- 4 Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35233, USA
- 5 Nathan Shock Center of Excellence in the Basic Biology of Aging, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- 6 Department of Applied Health Sciences, Indiana University, School of Public Health-Bloomington, Bloomington, IN 47405, USA
- 7 Present Address: University of Arkansas for Medical Sciences and Arkansas Children’s Research Institute, Little Rock, AR 72202, USA
- 8 Department of Biology, Jacksonville State University, Jacksonville, AL 36265, USA
- 9 Center for Convergent Bioscience and Medicine, University of Alabama, Tuscaloosa, AL 35401, USA
- 10 Alabama Life Research Institute, University of Alabama, Tuscaloosa, AL 35401, USA
Received: October 20, 2022 Accepted: February 20, 2023 Published: March 22, 2023
https://doi.org/10.18632/aging.204593How to Cite
Copyright: © 2023 Hagedorn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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 Drosophila melanogaster 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.
Abbreviations
FHV: Flock House Virus; OCR: Oxygen Consumption Rate; RNAi: RNA interference; siRNA: small interfering RNA pathway; H3K9: H3 lysine K9; DCV: Drosophila C Virus; OXPHOS: oxidative phosphorylation; ATP: adenosine 5’ triphosphate; LDH: lactate dehydrogenase; CO2: carbon dioxide; Ni: Non-injected; ZT: Zeitgeber Time; Cct: Phosphocholine cytidylyltransferase; AGEs: advanced glycation end products; COEC: Comparative Organismal Energetics Core; TCID50: 50% Tissue Culture Infective Dose.