Differential neurovirulence of Usutu virus lineages in mice and neuronal cells

Journal of Neuroinflammation

Daniel Cadar¹  Jonas Schmidt-Chanasit²  Caroline Desmetz³  Fabien Gosselet⁴  Juan-Carlos Saiz⁵  Liana Teodori⁶  Giovanni Savini⁶  Federica Monaco⁶  Sara Salinas⁷  Marion Clé⁷  Yannick Simonin⁷  Orianne Constant⁷  Jonathan Barthelemy⁷  Vincent Foulongne⁸  Philippe Van de Perre⁸  Cécile Beck⁹  Sylvie Lecollinet⁹  Gaëlle Gonzales⁹  Lina Lapeyre^1,10  Marie France Martin^1,10 

[1] Bernhard Nocht Institute for Tropical Medicine, WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research, 20359, Hamburg, Germany;Bernhard Nocht Institute for Tropical Medicine, WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research, 20359, Hamburg, Germany;Faculty of Mathematics, Informatics and Natural Sciences, Universität Hamburg, 20148, Hamburg, Germany;BioCommunication en CardioMétabolique (BC2M), Montpellier University, Montpellier, France;Blood-Brain Barrier Laboratory (BBB Lab), University of Artois, UR2465, F-62300, Lens, France;Department of Biotechnology, INIA, Madrid, Spain;OIE Reference Centre for West Nile Disease, Istituto Zooprofilattico Sperimentale “G. Caporale”, 46100, Teramo, Italy;Pathogenesis and Control of Chronic Infections, Université de Montpellier, INSERM, EFS, Montpellier, France;Pathogenesis and Control of Chronic Infections, Université de Montpellier, INSERM, EFS, Montpellier, France;Centre Hospitalier Universitaire de Montpellier, Montpellier, France;UPE, Anses Animal Health Laboratory, UMR1161 Virology, INRA, Anses, ENVA, Maisons-Alfort, France;Université de Montpellier, CNRS, Viral Trafficking, Restriction and Innate Signaling, Montpellier, France;

关键词: Usutu virus;    Arbovirus;    Flavivirus;    Neurotropism;    Central nervous system;   

DOI  :  10.1186/s12974-020-02060-4

来源: Springer

【 摘 要 】

BackgroundUsutu virus (USUV) is an emerging neurotropic arthropod-borne virus recently involved in massive die offs of wild birds predominantly reported in Europe. Although primarily asymptomatic or presenting mild clinical signs, humans infected by USUV can develop neuroinvasive pathologies (including encephalitis and meningoencephalitis). Similar to other flaviviruses, such as West Nile virus, USUV is capable of reaching the central nervous system. However, the neuropathogenesis of USUV is still poorly understood, and the virulence of the specific USUV lineages is currently unknown. One of the major complexities of the study of USUV pathogenesis is the presence of a great diversity of lineages circulating at the same time and in the same location.MethodsThe aim of this work was to determine the neurovirulence of isolates from the six main lineages circulating in Europe using mouse model and several neuronal cell lines (neurons, microglia, pericytes, brain endothelial cells, astrocytes, and in vitro Blood-Brain Barrier model).ResultsOur results indicate that all strains are neurotropic but have different virulence profiles. The Europe 2 strain, previously described as being involved in several clinical cases, induced the shortest survival time and highest mortality in vivo and appeared to be more virulent and persistent in microglial, astrocytes, and brain endothelial cells, while also inducing an atypical cytopathic effect. Moreover, an amino acid substitution (D3425E) was specifically identified in the RNA-dependent RNA polymerase domain of the NS5 protein of this lineage.ConclusionsAltogether, these data show a broad neurotropism for USUV in the central nervous system with lineage-dependent virulence. Our results will help to better understand the biological and epidemiological diversity of USUV infection.

【 授权许可】

CC BY