Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
Schreiner P, Harrer T, Scheibenbogen C, Lamer S, Schlosser A, Naviaux R, Prusty BK (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 4
Pages Range: 201-215
Journal Issue: 4
DOI: 10.4049/immunohorizons.2000006
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifactorial disorder with many possible triggers. Human herpesvirus (HHV)-6 and HHV-7 are two infectious triggers for which evidence has been growing. To understand possible causative role of HHV-6 in ME/CFS, metabolic and antiviral phenotypes of U2-OS cells were studied with and without chromosomally integrated HHV-6 and with or without virus reactivation using the histone deacetylase inhibitor trichostatin-A. Proteomic analysis was conducted by pulsed stable isotope labeling by amino acids in cell culture analysis. Antiviral properties that were induced by HHV-6 transactivation were studied in virus-naive A549 cells challenged by infection with influenza-A (H1N1) or HSV-1. Mitochondria were fragmented and 1-carbon metabolism, dUTPase, and thymidylate synthase were strongly induced by HHV-6 reactivation, whereas superoxide dismutase 2 and proteins required for mitochondrial oxidation of fatty acid, amino acid, and glucose metabolism, including pyruvate dehydrogenase, were strongly inhibited. Adoptive transfer of U2-OS cell supernatants after reactivation of HHV-6A led to an antiviral state in A549 cells that prevented superinfection with influenza-A and HSV-1. Adoptive transfer of serum from 10 patients with ME/CFS produced a similar fragmentation of mitochondria and the associated antiviral state in the A549 cell assay. In conclusion, HHV-6 reactivation in ME/CFS patients activates a multisystem, proinflammatory, cell danger response that protects against certain RNA and DNA virus infections but comes at the cost of mitochondrial fragmentation and severely compromised energy metabolism.
Authors with CRIS profile
Involved external institutions
Julius-Maximilians-Universität Würzburg
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
University of California, San Diego
United States (USA) (US)
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
University of California, San Diego
United States (USA) (US)
How to cite
APA:
Schreiner, P., Harrer, T., Scheibenbogen, C., Lamer, S., Schlosser, A., Naviaux, R., & Prusty, B.K. (2020). Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. ImmunoHorizons, 4(4), 201-215. https://doi.org/10.4049/immunohorizons.2000006
MLA:
Schreiner, Philipp, et al. "Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome." ImmunoHorizons 4.4 (2020): 201-215.
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