Identification of Umbre Orthobunyavirus as a Novel Zoonotic Virus Responsible for Lethal Encephalitis in 2 French Patients With Hypogammaglobulinemia

Philippe Perot (1) , Franck Bielle (2, 3) , Thomas Bigot (4) , Vincent Foulongne (5, 6, 7) , Karine Bolloré (5, 6) , Delphine Chrétien (1) , Patricia Gil (8, 9) , Serafin Gutierrez (8, 9) , Grégory L’ambert (10) , Karima Mokhtari (2, 3) , Jan Hellert (11) , Marie Flamand (11) , Carole Tamietti (11) , Muriel Coulpier (12) , Anne Huard de Verneuil (12) , Sarah Temmam (1) , Thérèse Couderc (13) , Edouard de Sousa Cunha (2) , Susana Boluda (2, 3, 14, 15) , Isabelle Plu (2, 3, 14, 15) , Marie Bernadette Delisle (16) , Fabrice Bonneville (16, 17) , David Brassat (18, 19) , Claire Fieschi (20) , Marion Malphettes (20) , Charles Duyckaerts (3, 2) , Bertrand Mathon (3, 21) , Sophie Demeret (22) , Danielle Seilhean (2, 3, 14, 15) , Marc Eloit (1, 23)

1 Découverte de pathogènes – Pathogen discovery
2 Laboratoire de Neuropathologie Raymond Escourolle [CHU Pitié-Salpétriêre]
3 ICM - Institut du Cerveau = Paris Brain Institute
4 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB
5 Etablissement français du don du sang [Montpellier]
6 PCCEI - Pathogenesis and Control of Chronic and Emerging Infections
7 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
8 UMR ASTRE - Animal, Santé, Territoires, Risques et Ecosystèmes
9 Cirad-BIOS - Département Systèmes Biologiques
10 EID - Entente Interdépartementale pour la démoustication du littoral méditerranéen
11 Virologie Structurale - Structural Virology
12 VIRO - Virologie UMR1161
13 Biologie des Infections - Biology of Infection
14 Centre national de référence des Agents Transmissibles Non Conventionnels
15 Santé publique France - French National Public Health Agency [Saint-Maurice, France]
16 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
17 ToNIC - Toulouse Neuro Imaging Center
18 CPTP - Centre de Physiopathologie Toulouse Purpan
19 Pôle Neurosciences [CHU Toulouse]
20 Service d'Immunopathologie [Hôpital Saint-Louis, Paris]
21 CHU Charles Foix [AP-HP]
22 CIC Neurosciences - Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière]
23 ENVA - École nationale vétérinaire - Alfort

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.

Keywords: metatranscriptomics; next-generation sequencing; Umbre virus; orthobunyavirus; encephalitis

Domains: Life Sciences [q-bio]; Human health and pathology; Infectious diseases; Life Sciences [q-bio]; Microbiology and Parasitology; Virology; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Genomics [q-bio.GN]; Life Sciences [q-bio]; Human health and pathology; Tissues and Organs [q-bio.TO]; Environmental Sciences; Global Changes

Philippe Perot, Franck Bielle, Thomas Bigot, Vincent Foulongne, Karine Bolloré, et al.. Identification of Umbre Orthobunyavirus as a Novel Zoonotic Virus Responsible for Lethal Encephalitis in 2 French Patients With Hypogammaglobulinemia. Clinical Infectious Diseases, 2021, 72 (10), pp.1701-1708. ⟨10.1093/cid/ciaa308⟩. ⟨pasteur-02863210⟩