David J Beale1, Ding Yuan Oh2,3, Avinash V Karpe4, Celeste Tai5, Michael S Dunn6, Danielle Tilmanis5, Enzo A Palombo7, Aeron C Hurt5,8. 1. Commonwealth Scientific & Industrial Research Organization (CSIRO), Land & Water, P.O. Box 2583, Brisbane, QLD, 4001, Australia. David.Beale@csiro.au. 2. WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia. Dingyuan.oh@gmail.com. 3. School of Health and Life Sciences, Federation University, Churchill, VIC, Australia. Dingyuan.oh@gmail.com. 4. Commonwealth Scientific & Industrial Research Organization (CSIRO), Land & Water, P.O. Box 2583, Brisbane, QLD, 4001, Australia. 5. WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia. 6. Analytical Science and Technology, Seqirus, Parkville, VIC, 3052, Australia. 7. Faculty of Science, Engineering and Technology, Swinburne University of Technology, PO Box 218, Hawthorn, VIC, 3122, Australia. 8. Department of Microbiology and Immunology, University of Melbourne, Parkville, VIC, Australia.
Abstract
INTRODUCTION: Influenza is a highly contagious respiratory disease that causes high global morbidity and mortality each year. The dynamics of an influenza infection on the host metabolism, and how metabolism is altered in response to neuraminidase inhibitor drug therapy, is still in its infancy but of great importance. OBJECTIVES: We aim to investigate the suitability of ferret nasal wash samples for metabolomics-based analysis and characterization of influenza infections and oseltamivir treatment. METHODS: Virological and metabolic analyses were performed on nasal wash samples collected from ferrets treated with oseltamivir or a placebo. Untargeted metabolomics was performed using a gas chromatography coupled with mass spectrometery (GC-MS) based protocol that comprised a retention time (RT) locked method and the use of a commercial metabolomics library. RESULTS: Ferret activity was reduced at 2-3 days post infection, which coincided with the highest influenza viral titre. The metabolomics data indicated a shift in metabolism during various stages of infection. The neuraminidase inhibitor oseltamivir created considerable downregulation of energy center metabolites (glucose, sucrose, glycine and glutamine), which generated high levels of branched amino acids. This further increased branched amino acid degradation and deregulation via glycerate-type intermediates and biosynthesis of fatty acids in oseltamivir-treated animals where abrogated weight loss was observed. CONCLUSION: Metabolomics was used to profile influenza infection and antiviral drug treatment in ferrets. This has the potential to provide indicators for the early diagnosis of influenza infection and assess the effectiveness of drug therapies.
INTRODUCTION:Influenza is a highly contagious respiratory disease that causes high global morbidity and mortality each year. The dynamics of an influenza infection on the host metabolism, and how metabolism is altered in response to neuraminidase inhibitor drug therapy, is still in its infancy but of great importance. OBJECTIVES: We aim to investigate the suitability of ferret nasal wash samples for metabolomics-based analysis and characterization of influenza infections and oseltamivir treatment. METHODS: Virological and metabolic analyses were performed on nasal wash samples collected from ferrets treated with oseltamivir or a placebo. Untargeted metabolomics was performed using a gas chromatography coupled with mass spectrometery (GC-MS) based protocol that comprised a retention time (RT) locked method and the use of a commercial metabolomics library. RESULTS:Ferret activity was reduced at 2-3 days post infection, which coincided with the highest influenza viral titre. The metabolomics data indicated a shift in metabolism during various stages of infection. The neuraminidase inhibitor oseltamivir created considerable downregulation of energy center metabolites (glucose, sucrose, glycine and glutamine), which generated high levels of branched amino acids. This further increased branched amino acid degradation and deregulation via glycerate-type intermediates and biosynthesis of fatty acids in oseltamivir-treated animals where abrogated weight loss was observed. CONCLUSION: Metabolomics was used to profile influenza infection and antiviral drug treatment in ferrets. This has the potential to provide indicators for the early diagnosis of influenza infection and assess the effectiveness of drug therapies.
Authors: David J Beale; Oliver A H Jones; Avinash V Karpe; Saravanan Dayalan; Ding Yuan Oh; Konstantinos A Kouremenos; Warish Ahmed; Enzo A Palombo Journal: Int J Mol Sci Date: 2016-12-23 Impact factor: 5.923
Authors: Snehal R Jadhav; Rohan M Shah; Avinash V Karpe; Robert S Barlow; Kate E McMillan; Michelle L Colgrave; David J Beale Journal: Metabolites Date: 2021-01-25
Authors: David J Beale; Rohan Shah; Avinash V Karpe; Katie E Hillyer; Alexander J McAuley; Gough G Au; Glenn A Marsh; Seshadri S Vasan Journal: Metabolites Date: 2021-05-19
Authors: Avinash V Karpe; Melanie L Hutton; Steven J Mileto; Meagan L James; Chris Evans; Rohan M Shah; Amol B Ghodke; Katie E Hillyer; Suzanne S Metcalfe; Jian-Wei Liu; Tom Walsh; Dena Lyras; Enzo A Palombo; David J Beale Journal: Metabolites Date: 2021-06-11