Philippe Pérot1, Franck Bielle2,3, Thomas Bigot4, Vincent Foulongne5, Karine Bolloré5, Delphine Chrétien1, Patricia Gil6,7, Serafín Gutiérrez6,7, Grégory L'Ambert8, Karima Mokhtari2,3, Jan Hellert9, Marie Flamand9, Carole Tamietti9, Muriel Coulpier10, Anne Huard de Verneuil10, Sarah Temmam1, Thérèse Couderc11, Edouard De Sousa Cunha2, Susana Boluda2,3,12, Isabelle Plu2,3,12, Marie Bernadette Delisle13, Fabrice Bonneville14, David Brassat15, Claire Fieschi16, Marion Malphettes16, Charles Duyckaerts2,3, Bertrand Mathon3,17, Sophie Demeret18, Danielle Seilhean2,3,12, Marc Eloit1,19. 1. Pathogen Discovery Laboratory, Institut Pasteur, Paris, France. 2. Département de Neuropathologie Raymond Escourolle, Assistance Publique - Hôpitaux de Paris (AP-HP)-Sorbonne, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. 3. Sorbonne Université, Brain Institute (Institut du Cerveau et de la Moelle épinière; Institut National de la Santé et de la Recherche Médicale [INSERM], Unité Mixte de Recherche Santé 1127; Centre National de la Recherche Scientifique [CNRS], Unité Mixte de Recherche [UMR] 7225), Paris, France. 4. Hub de Bioinformatique et Biostatistique - Département Biologie Computationnelle, Institut Pasteur, Unité de Service et de Recherche 3756 CNRS, Paris, France. 5. Pathogenesis and Control of Chronic Infections, INSERM, University of Montpellier, Etablissement Français du Sang, Centre Hospitalier Universitaire (CHU) Montpellier, Montpellier, France. 6. Centre de Coopération Internationale en Recherche Agronomique Pour le Développement (CIRAD), UMR ASTRE, Montpellier, France. 7. ASTRE, CIRAD, Institut National de la Recherche Agronomique, University of Montpellier, Montpellier, France. 8. Entente Interdépartementale Pour la Démoustication Méditerranée, Montpellier, France. 9. Structural Virology Unit, Institut Pasteur, CNRS UMR 3569, Paris, France. 10. UMR Virologie, Agence Nationale de Sécurité Sanitaire de l'Alimentation, de l'Environnement et du Travail, École Nationale Vétérinaire d'Alfort, Institut National de Recherche Pour l'Agriculture, l'Alimentation et l'Environnement, Université Paris Est, Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort, France. 11. Biology of Infection Unit, Institut Pasteur, INSERM U1117, Paris, France. 12. Centre National de Référence des Agents Transmissibles Non Conventionnels (Reference Center for Nonconventional Transmissible Agents), Laboratory and Neuropathology Network for the Surveillance of Creutzfeldt-Jakob Disease, Santé Publique France, AP-HP, Paris, France. 13. Laboratoire de Neuropathologie, Laboratoire Universitaire d'Anatomie et Cytologie Pathologiques, CHU de Toulouse, Université Toulouse III-Paul Sabatier, Toulouse, France. 14. Department of Neuroradiology, CHU de Toulouse and UMR 1214 Toulouse NeuroImaging Center, Université de Toulouse, INSERM, Toulouse, France. 15. Centre de Ressources et de Compétences Sclérose en Plaques, Pole des Neurosciences CHU Toulouse and UMR 1043, Université de Toulouse III, Toulouse, France. 16. Service d'Immunologie Clinique, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France. 17. AP-HP, Hôpitaux Universitaires Pitié-Salpêtrière Charles-Foix, Department of Neurosurgery, Paris, France. 18. Department of Neurology, Neuro ICU, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France. 19. Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort, France.
Abstract
BACKGROUND: Human encephalitis represents a medical challenge from a diagnostic and therapeutic point of view. We investigated the cause of 2 fatal cases of encephalitis of unknown origin in immunocompromised patients. METHODS: Untargeted metatranscriptomics was applied on the brain tissue of 2 patients to search for pathogens (viruses, bacteria, fungi, or protozoans) without a prior hypothesis. RESULTS: Umbre arbovirus, an orthobunyavirus never previously identified in humans, was found in 2 patients. In situ hybridization and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) showed that Umbre virus infected neurons and replicated at high titers. The virus was not detected in cerebrospinal fluid by RT-qPCR. Viral sequences related to Koongol virus, another orthobunyavirus close to Umbre virus, were found in Culex pipiens mosquitoes captured in the south of France where the patients had spent some time before the onset of symptoms, demonstrating the presence of the same clade of arboviruses in Europe and their potential public health impact. A serological survey conducted in the same area did not identify individuals positive for Umbre virus. The absence of seropositivity in the population may not reflect the actual risk of disease transmission in immunocompromised individuals. CONCLUSIONS: Umbre arbovirus can cause encephalitis in immunocompromised humans and is present in Europe.
BACKGROUND:Humanencephalitis represents a medical challenge from a diagnostic and therapeutic point of view. We investigated the cause of 2 fatal cases of encephalitis of unknown origin in immunocompromised patients. METHODS: Untargeted metatranscriptomics was applied on the brain tissue of 2 patients to search for pathogens (viruses, bacteria, fungi, or protozoans) without a prior hypothesis. RESULTS: Umbre arbovirus, an orthobunyavirus never previously identified in humans, was found in 2 patients. In situ hybridization and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) showed that Umbre virusinfected neurons and replicated at high titers. The virus was not detected in cerebrospinal fluid by RT-qPCR. Viral sequences related to Koongol virus, another orthobunyavirus close to Umbre virus, were found in Culex pipiens mosquitoes captured in the south of France where the patients had spent some time before the onset of symptoms, demonstrating the presence of the same clade of arboviruses in Europe and their potential public health impact. A serological survey conducted in the same area did not identify individuals positive for Umbre virus. The absence of seropositivity in the population may not reflect the actual risk of disease transmission in immunocompromised individuals. CONCLUSIONS: Umbre arbovirus can cause encephalitis in immunocompromised humans and is present in Europe.
Authors: Jennifer A Bohl; Sreyngim Lay; Sophana Chea; Vida Ahyong; Daniel M Parker; Shannon Gallagher; Jonathan Fintzi; Somnang Man; Aiyana Ponce; Sokunthea Sreng; Dara Kong; Fabiano Oliveira; Katrina Kalantar; Michelle Tan; Liz Fahsbender; Jonathan Sheu; Norma Neff; Angela M Detweiler; Christina Yek; Sokna Ly; Rathanak Sath; Chea Huch; Hok Kry; Rithea Leang; Rekol Huy; Chanthap Lon; Cristina M Tato; Joseph L DeRisi; Jessica E Manning Journal: Proc Natl Acad Sci U S A Date: 2022-03-01 Impact factor: 11.205
Authors: Francis R Hopkins; Beatriz Álvarez-Rodríguez; George R Heath; Kyriakoulla Panayi; Samantha Hover; Thomas A Edwards; John N Barr; Juan Fontana Journal: mBio Date: 2022-06-28 Impact factor: 7.786