| Autor: |
Scheiber C; Clinic for Anaesthesiology and Intensive Care Medicine, Ulm University Hospital, 89081 Ulm, Germany.; Department of Neurology, Ulm University Hospital, 89081 Ulm, Germany., Klein HC; Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.; Research and Education Department Addiction Care Northern Netherlands, 9728 JR Groningen, The Netherlands., Schneider JM; Clinic for Anaesthesiology and Intensive Care Medicine, Ulm University Hospital, 89081 Ulm, Germany., Schulz T; Clinic for Anaesthesiology and Intensive Care Medicine, Ulm University Hospital, 89081 Ulm, Germany., Bechter K; Clinic for Psychiatry and Psychotherapy II, Ulm University, 89312 Guenzburg, Germany., Tumani H; Department of Neurology, Ulm University Hospital, 89081 Ulm, Germany., Kapapa T; Department of Neurosurgery, Ulm University Hospital, 89081 Ulm, Germany., Flinkman D; Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20521 Turku, Finland., Coffey E; Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20521 Turku, Finland., Ross D; Kimera Labs Inc., Miramar, FL 33025, USA., Čistjakovs M; Institute of Microbiology and Virology, Riga Stradins University, 1067 Riga, Latvia., Nora-Krūkle Z; Institute of Microbiology and Virology, Riga Stradins University, 1067 Riga, Latvia., Bortolotti D; Department of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, Via Luigi Borsari, 46, 44121 Ferrara, Italy., Rizzo R; Department of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, Via Luigi Borsari, 46, 44121 Ferrara, Italy.; Laboratory for Advanced Therapeutic Technologies (LTTA), University of Ferrara, 44121 Ferrara, Italy., Murovska M; Institute of Microbiology and Virology, Riga Stradins University, 1067 Riga, Latvia., Schneider EM; Clinic for Anaesthesiology and Intensive Care Medicine, Ulm University Hospital, 89081 Ulm, Germany.; Department of Neurology, Ulm University Hospital, 89081 Ulm, Germany. |
| Abstrakt: |
Virus-associated chronic inflammation may contribute to autoimmunity in a number of diseases. In the brain, autoimmune encephalitis appears related to fluctuating reactivation states of neurotropic viruses. In addition, viral miRNAs and proteins can be transmitted via exosomes, which constitute novel but highly relevant mediators of cellular communication. The current study questioned the role of HSV-1-encoded and host-derived miRNAs in cerebrospinal fluid (CSF)-derived exosomes, enriched from stress-induced neuroinflammatory diseases, mainly subarachnoid hemorrhage (SAH), psychiatric disorders (AF and SZ), and various other neuroinflammatory diseases. The results were compared with CSF exosomes from control donors devoid of any neuroinflammatory pathology. Serology proved positive, but variable immunity against herpesviruses in the majority of patients, except controls. Selective ultrastructural examinations identified distinct, herpesvirus-like particles in CSF-derived lymphocytes and monocytes. The likely release of extracellular vesicles and exosomes was most frequently observed from CSF monocytes. The exosomes released were structurally similar to highly purified stem-cell-derived exosomes. Exosomal RNA was quantified for HSV-1-derived miR-H2-3p, miR-H3-3p, miR-H4-3p, miR-H4-5p, miR-H6-3p, miR-H27 and host-derived miR-21-5p, miR-146a-5p, miR-155-5p, and miR-138-5p and correlated with the oxidative stress chemokine IL-8 and the axonal damage marker neurofilament light chain (NfL). Replication-associated miR-H27 correlated with neuronal damage marker NfL, and cell-derived miR-155-5p correlated with oxidative stress marker IL-8. Elevated miR-138-5p targeting HSV-1 latency-associated ICP0 inversely correlated with lower HSV-1 antibodies in CSF. In summary, miR-H27 and miR-155-5p may constitute neuroinflammatory markers for delineating frequent and fluctuating HSV-1 replication and NfL-related axonal damage in addition to the oxidative stress cytokine IL-8 in the brain. Tentatively, HSV-1 remains a relevant pathogen conditioning autoimmune processes and a psychiatric clinical phenotype. |
