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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, * 
* Corresponding author
6 PCCEI - Pathogenesis and Control of Chronic and Emerging Infections
INSERM - Institut National de la Santé et de la Recherche Médicale : U 1058, UM - Université de Montpellier, UA - Université des Antilles, Etablissement français du don du sang [Montpellier]
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.
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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, Oxford University Press (OUP), 2021, 72 (10), pp.1701-1708. ⟨10.1093/cid/ciaa308⟩. ⟨pasteur-02863210⟩

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