Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
| Autor: | Stephanie Lamer, Robert K. Naviaux, Philipp Schreiner, Thomas Harrer, Bhupesh K. Prusty, Andreas Schlosser, Carmen Scheibenbogen |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Adoptive cell transfer medicine.drug_class Herpesvirus 6 Human viruses Encephalomyelitis Immunology Cell Roseolovirus Infections Herpesvirus 7 Human Herpesvirus 1 Human Mitochondrion Virus Microbiology Young Adult Influenza A Virus H1N1 Subtype Influenza Human medicine Humans Immunology and Allergy Fragmentation (cell biology) Fatigue Syndrome Chronic Chemistry Histone deacetylase inhibitor virus diseases Herpes Simplex General Medicine Middle Aged Pyruvate dehydrogenase complex medicine.disease Adoptive Transfer Immunity Innate Mitochondria Phenotype medicine.anatomical_structure A549 Cells DNA Viral Female Virus Activation |
| Zdroj: | ImmunoHorizons. 4:201-215 |
| ISSN: | 2573-7732 |
| DOI: | 10.4049/immunohorizons.2000006 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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