Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants.

Autor: de Melo GD; Institut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit, F-75015, Paris, France., Perraud V; Institut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit, F-75015, Paris, France., Alvarez F; Institut Pasteur, Université Paris Cité, Channel Receptors Unit, F-75015, Paris, France.; Sorbonne Université, Collège Doctoral, F-75005, Paris, France., Vieites-Prado A; Institut du Cerveau et de la Moelle Épinière, Laboratoire de Plasticité Structurale, , Sorbonne Université, INSERM U1127, CNRS UMR7225, 75013, Paris, France., Kim S; Institut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit, F-75015, Paris, France., Kergoat L; Institut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit, F-75015, Paris, France., Coleon A; Institut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit, F-75015, Paris, France., Trüeb BS; Institute of Virology and Immunology (IVI), Bern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Tichit M; Institut Pasteur, Université Paris Cité, Histopathology Platform, F-75015, Paris, France., Piazza A; Institut Pasteur, Université Paris Cité, Spatial Regulation of Genomes Laboratory, F-75015, Paris, France., Thierry A; Institut Pasteur, Université Paris Cité, Spatial Regulation of Genomes Laboratory, F-75015, Paris, France., Hardy D; Institut Pasteur, Université Paris Cité, Histopathology Platform, F-75015, Paris, France., Wolff N; Institut Pasteur, Université Paris Cité, Channel Receptors Unit, F-75015, Paris, France., Munier S; Institut Pasteur, Université Paris Cité, Molecular Genetics of RNA viruses Unit, F-75015, Paris, France., Koszul R; Institut Pasteur, Université Paris Cité, Spatial Regulation of Genomes Laboratory, F-75015, Paris, France., Simon-Lorière E; Institut Pasteur, Université Paris Cité, Evolutionary Genomics of RNA Viruses Group, F-75015, Paris, France., Thiel V; Multidisciplinary Center for Infectious Diseases, University of Bern, Bern, Switzerland., Lecuit M; Institut Pasteur, Université Paris Cité, Inserm U1117, Biology of Infection Unit, 75015, Paris, France.; Necker-Enfants Malades University Hospital, Division of Infectious Diseases and Tropical Medicine, APHP, Institut Imagine, 75006, Paris, France., Lledo PM; Institut Pasteur, Université Paris Cité, Perception and Memory Unit, F-75015 Paris, France; CNRS UMR3571, 75015, Paris, France., Renier N; Institut du Cerveau et de la Moelle Épinière, Laboratoire de Plasticité Structurale, , Sorbonne Université, INSERM U1127, CNRS UMR7225, 75013, Paris, France., Larrous F; Institut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit, F-75015, Paris, France., Bourhy H; Institut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit, F-75015, Paris, France. herve.bourhy@pasteur.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Jul 26; Vol. 14 (1), pp. 4485. Date of Electronic Publication: 2023 Jul 26.
DOI: 10.1038/s41467-023-40228-7
Abstrakt: Anosmia was identified as a hallmark of COVID-19 early in the pandemic, however, with the emergence of variants of concern, the clinical profile induced by SARS-CoV-2 infection has changed, with anosmia being less frequent. Here, we assessed the clinical, olfactory and neuroinflammatory conditions of golden hamsters infected with the original Wuhan SARS-CoV-2 strain, its isogenic ORF7-deletion mutant and three variants: Gamma, Delta, and Omicron/BA.1. We show that infected animals develop a variant-dependent clinical disease including anosmia, and that the ORF7 of SARS-CoV-2 contributes to the induction of olfactory dysfunction. Conversely, all SARS-CoV-2 variants are neuroinvasive, regardless of the clinical presentation they induce. Taken together, this confirms that neuroinvasion and anosmia are independent phenomena upon SARS-CoV-2 infection. Using newly generated nanoluciferase-expressing SARS-CoV-2, we validate the olfactory pathway as a major entry point into the brain in vivo and demonstrate in vitro that SARS-CoV-2 travels retrogradely and anterogradely along axons in microfluidic neuron-epithelial networks.
(© 2023. The Author(s).)
Databáze: MEDLINE
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