1. Pathogenesis of recent Lassa virus isolates from lineages II and VII in cynomolgus monkeys
- Author
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Mateo, Mathieu, Hortion, Jimmy, Perthame, Emeline, Picard, Caroline, Reynard, Stéphanie, Journeaux, Alexandra, Germain, Clara, Carnec, Xavier, Baillet, Nicolas, Borges-Cardoso, Virginie, Pietrosemoli, Natalia, Vallve, Audrey, Barron, Stéphane, Jourjon, Ophélie, Lacroix, Orianne, Duthey, Aurélie, Dirheimer, Manon, Daniau, Maïlys, Legras-Lachuer, Catherine, Jouvion, Gregory, Carbonnelle, Caroline, Raoul, Hervé, Baize, Sylvain, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Laboratoire P4 - Jean Mérieux, Centre Européen de Virologie/Immunologie-Institut National de la Santé et de la Recherche Médicale (INSERM), ViroScan3D SAS [Trévoux, France], Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), MATEO, MATHIEU, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Université Paris Cité (UPCité), and Institut Pasteur [Paris]-Université Paris Cité (UPCité)
- Subjects
Microbiology (medical) ,cynomolgus monkeys ,Immunology ,viral hemorrhagic fevers ,MESH: Lassa Fever ,Virus Replication ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,Microbiology ,Lassa Fever ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Animals ,Humans ,MESH: Animals ,Lassa virus ,[SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity ,[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,MESH: Humans ,pathogenesis ,MESH: Virus Replication ,MESH: Lassa virus ,immune responses ,Macaca fascicularis ,Infectious Diseases ,MESH: Macaca fascicularis ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Parasitology - Abstract
We thank P. Regnard, P.H. Moreau, and L. Fellmann (SILABE, Strasbourg) for medical care given to the monkeys. We thank S. Mundweiller, S. Godard, E. Moissonnier, D. Thomas, S. Mely, B. Labrosse, D. Pannetier, and C. Leculier (P4 INSERM–Jean Merieux, US003, INSERM) for assistance in conducting the BSL-4 experiments. We thank M-A Dillies (HUB, Institut Pasteur) for helpful discussions. We thank G. Fourcaud and B. Lafoux (UBIVE, CIRI, Institut Pasteur) for technical help. We also thank L. Branco (Zalgen Labs) for providing recombinant proteins. We are grateful to the Coalition for Epidemic Preparedness and Innovations (R. Hatchett, G. Thiry, and M. Saville) and C. Gerke (Department of Innovation Development, Institut Pasteur) for invaluable support.; International audience; The area of Lassa virus (LASV) circulation is expanding, with the emergence of highly pathogenic new LASV lineages. Benin recently became an endemic country for LASV and has seen the emergence of a new LASV lineage (VII). The first two outbreaks in 2014 and 2016 showed a relatively high mortality rate compared to other outbreaks. We infected cynomolgus monkeys with two strains belonging to lineage II and lineage VII that were isolated from deceased patients during the 2016 outbreak in Benin. The lineage VII strain (L7) caused uniform mortality. Death was associated with uncontrolled viral replication, unbalanced inflammatory responses characterized by increased concentrations of pro- and anti-inflammatory mediators, and the absence of efficient immune responses, resembling the pathogenesis associated with the prototypic Josiah strain in monkeys. The lineage II strain (L2) showed apparently lower virulence than its counterpart, with a prolonged time to death and a lower mortality rate. Prolonged survival was associated with better control of viral replication, a moderate inflammatory response, and efficient T-cell responses. Transcriptomic analyses also highlighted important differences in the immune responses associated with the outcome. Both strains caused strong inflammation in several organs. Notably, meningitis and encephalitis were observed in the cerebral cortex and cerebellum in all monkeys, independently of the outcome. Due to their apparently high pathogenicity, emerging strains from lineage VII should be considered in preclinical vaccine testing. Lineage II would also be beneficial in pathogenesis studies to study the entire spectrum of Lassa fever severity.
- Published
- 2022