Summary of the project
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifactorial disease with many triggers. Growing epidemiological evidence suggests that human herpesvirus 6 (HHV-6) and HHV-7 are two highly probable infectious triggers for ME/CFS. Using a unique model for latent HHV-6 cells, we recently observed several overlapping phenotypes that have also been observed in ME/CFS patients. The most convincing phenotypes include fragmented mitochondria, induced 1-carbon metabolism, dUTPase, thymidylate synthase, and reduced superoxide dismutase 2, mitochondrial oxidation of fatty acids, amino acids, and glucose metabolism via pyruvate dehydrogenase pathways. Furthermore, adoptive transfer of virus-reactivated cell supernatants and ME/CFS patient serum led to an antiviral state in A549 cells, which prevented superinfection with influenza A and HSV-1. Based on these findings, we propose that various infections, including HHV-6 reactivation in ME/CFS patients, trigger a multisystemic, proinflammatory, cellular danger response that protects host cells from certain RNA and DNA viral infections, but at the cost of mitochondrial fragmentation and severely impaired energy metabolism. As a continuation of our research, we propose several different methods that will enable us to develop two potential diagnostic tests for ME/CFS and develop potential drugs that can reverse the phenotype of mitochondrial dysfunction.
Name and affiliation of the PI:
Dr. Bhupesh K Prusty Senior Researcher
Versbacher Straße 7
97078 Würzburg
Germany
More information at
University of Würzburg
