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Browsing by Author "Ramonell, Katrina M"

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    Effects of Aging on Interactions Between Flock House Virus and a Drosophila Melanogaster Host
    (University of Alabama Libraries, 2025) Bunnell, Charles Dean; Chtarbanova, Stanislava
    RNA viruses pose a significant threat to human health, and individuals 65 and older are more susceptible to virus infection. Understanding the mechanisms underlying the aged organism's increased susceptibility is a major question in the field of immunology. A host's immune response and metabolic function must be coordinated to ensure an effective response to infection. In this dissertation, I utilized an aged Drosophila melanogaster host – Flock House virus (FHV) interactions model to investigate how the interplay between metabolism and immune function is affected with age. Whole-organism respirometry measured oxygen consumption rates (OCR) longitudinally after FHV infection at a single-fly resolution. Aged flies did not modulate OCRs after FHV infection, while young flies' OCR decreased longitudinally. I hypothesized that failure to modulate OCR in aged flies could impact their mortality and sought to investigate if interventions that decrease OCR extend survival of FHV. Mitochondria's bacterial ancestry renders them susceptible to tetracycline (TTC) and rifampicin (RIF) antibiotics, which disrupt mitochondrial translation and transcription respectively, causing mitochondrial dysfunction. This mild perturbation on mitochondria has been shown to induce the mitochondrial unfolded protein response (UPRmt) in mammalian studies and improved survival outcomes of infection. Diverse mitochondrial stressors including reactive oxygen species or defects in oxidative phosphorylation activate the UPRmt, which in turn acts to resolve the appropriate stressor. We find that TTC and RIF treatment extends survival of young and aged flies after FHV infection, without reducing FHV load, pointing to improved disease tolerance. We confirmed TTC's protection likely occurs independently of antimicrobial effects. TTC treatment increased expression of genes involved in UPRmt, glycolysis, and oxidative stress, which represents a transcriptional response typical of UPRmt activation. Finally, we find mutants of NADH dehydrogenase (ubiquinone) 23 kDa subunit (ND-23), which encodes a component of mitochondrial Complex I, display an extended end-point survival of FHV in comparison to wild-type controls. Our results suggest UPRmt activation induces disease tolerance that extends survival of virus infection. This work implicates UPRmt activation and host metabolism as potential therapeutic targets that require further investigations.