Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants
Abstract 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 con...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-07-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40228-7 |
| _version_ | 1827590522356629504 |
|---|---|
| author | Guilherme Dias de Melo Victoire Perraud Flavio Alvarez Alba Vieites-Prado Seonhee Kim Lauriane Kergoat Anthony Coleon Bettina Salome Trüeb Magali Tichit Aurèle Piazza Agnès Thierry David Hardy Nicolas Wolff Sandie Munier Romain Koszul Etienne Simon-Lorière Volker Thiel Marc Lecuit Pierre-Marie Lledo Nicolas Renier Florence Larrous Hervé Bourhy |
| author_facet | Guilherme Dias de Melo Victoire Perraud Flavio Alvarez Alba Vieites-Prado Seonhee Kim Lauriane Kergoat Anthony Coleon Bettina Salome Trüeb Magali Tichit Aurèle Piazza Agnès Thierry David Hardy Nicolas Wolff Sandie Munier Romain Koszul Etienne Simon-Lorière Volker Thiel Marc Lecuit Pierre-Marie Lledo Nicolas Renier Florence Larrous Hervé Bourhy |
| author_sort | Guilherme Dias de Melo |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-09T01:18:02Z |
| format | Article |
| id | doaj.art-dc7c96ca45ad44e181d1a009fdd44754 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-09T01:18:02Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-dc7c96ca45ad44e181d1a009fdd447542023-12-10T12:23:45ZengNature PortfolioNature Communications2041-17232023-07-0114111410.1038/s41467-023-40228-7Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variantsGuilherme Dias de Melo0Victoire Perraud1Flavio Alvarez2Alba Vieites-Prado3Seonhee Kim4Lauriane Kergoat5Anthony Coleon6Bettina Salome Trüeb7Magali Tichit8Aurèle Piazza9Agnès Thierry10David Hardy11Nicolas Wolff12Sandie Munier13Romain Koszul14Etienne Simon-Lorière15Volker Thiel16Marc Lecuit17Pierre-Marie Lledo18Nicolas Renier19Florence Larrous20Hervé Bourhy21Institut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology UnitInstitut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology UnitInstitut Pasteur, Université Paris Cité, Channel Receptors UnitInstitut du Cerveau et de la Moelle Épinière, Laboratoire de Plasticité Structurale, , Sorbonne Université, INSERM U1127Institut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology UnitInstitut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology UnitInstitut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology UnitInstitute of Virology and Immunology (IVI), Bern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of BernInstitut Pasteur, Université Paris Cité, Histopathology PlatformInstitut Pasteur, Université Paris Cité, Spatial Regulation of Genomes LaboratoryInstitut Pasteur, Université Paris Cité, Spatial Regulation of Genomes LaboratoryInstitut Pasteur, Université Paris Cité, Histopathology PlatformInstitut Pasteur, Université Paris Cité, Channel Receptors UnitInstitut Pasteur, Université Paris Cité, Molecular Genetics of RNA viruses UnitInstitut Pasteur, Université Paris Cité, Spatial Regulation of Genomes LaboratoryInstitut Pasteur, Université Paris Cité, Evolutionary Genomics of RNA Viruses GroupMultidisciplinary Center for Infectious Diseases, University of BernInstitut Pasteur, Université Paris Cité, Inserm U1117, Biology of Infection UnitInstitut Pasteur, Université Paris Cité, Perception and Memory Unit, F-75015 ParisInstitut du Cerveau et de la Moelle Épinière, Laboratoire de Plasticité Structurale, , Sorbonne Université, INSERM U1127Institut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology UnitInstitut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology UnitAbstract 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.https://doi.org/10.1038/s41467-023-40228-7 |
| spellingShingle | Guilherme Dias de Melo Victoire Perraud Flavio Alvarez Alba Vieites-Prado Seonhee Kim Lauriane Kergoat Anthony Coleon Bettina Salome Trüeb Magali Tichit Aurèle Piazza Agnès Thierry David Hardy Nicolas Wolff Sandie Munier Romain Koszul Etienne Simon-Lorière Volker Thiel Marc Lecuit Pierre-Marie Lledo Nicolas Renier Florence Larrous Hervé Bourhy Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants Nature Communications |
| title | Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants |
| title_full | Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants |
| title_fullStr | Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants |
| title_full_unstemmed | Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants |
| title_short | Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants |
| title_sort | neuroinvasion and anosmia are independent phenomena upon infection with sars cov 2 and its variants |
| url | https://doi.org/10.1038/s41467-023-40228-7 |
| work_keys_str_mv | AT guilhermediasdemelo neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT victoireperraud neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT flavioalvarez neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT albavieitesprado neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT seonheekim neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT laurianekergoat neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT anthonycoleon neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT bettinasalometrueb neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT magalitichit neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT aurelepiazza neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT agnesthierry neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT davidhardy neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT nicolaswolff neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT sandiemunier neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT romainkoszul neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT etiennesimonloriere neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT volkerthiel neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT marclecuit neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT pierremarielledo neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT nicolasrenier neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT florencelarrous neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants AT hervebourhy neuroinvasionandanosmiaareindependentphenomenauponinfectionwithsarscov2anditsvariants |