2. Academic Validation
  3. Evolution of SARS-CoV-2 in the murine central nervous system drives viral diversification

Evolution of SARS-CoV-2 in the murine central nervous system drives viral diversification

  • Nat Microbiol. 2024 Sep;9(9):2383-2394. doi: 10.1038/s41564-024-01786-8.
Jacob Class # 1,  Lacy M Simons # 2 3,  Ramon Lorenzo-Redondo 2 3,  Jazmin Galván Achi 1,  Laura Cooper 1,  Tanushree Dangi 4,  Pablo Penaloza-MacMaster 4,  Egon A Ozer 2 3,  Sarah E Lutz 5,  Lijun Rong 1,  Judd F Hultquist 6 7,  Justin M Richner 8
Affiliations

Affiliations

  • 1 Department of Microbiology and Immunology, College of Medicine, University of Illinois Chicago, Chicago, IL, USA.
  • 2 Department of Medicine, Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • 3 Center for Pathogen Genomics and Microbial Evolution, Havey Institute for Global Health, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • 4 Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • 5 Department of Anatomy and Cell Biology, College of Medicine, University of Illinois Chicago, Chicago, IL, USA.
  • 6 Department of Medicine, Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. judd.hultquist@northwestern.edu.
  • 7 Center for Pathogen Genomics and Microbial Evolution, Havey Institute for Global Health, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. judd.hultquist@northwestern.edu.
  • 8 Department of Microbiology and Immunology, College of Medicine, University of Illinois Chicago, Chicago, IL, USA. richner@uic.edu.
  • # Contributed equally.
PMID: 39179693 DOI: 10.1038/s41564-024-01786-8
Abstract

Severe coronavirus disease 2019 and post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Infection are associated with neurological complications that may be linked to direct Infection of the central nervous system (CNS), but the selective pressures ruling neuroinvasion are poorly defined. Here we assessed SARS-CoV-2 evolution in the lung versus CNS of infected mice. Higher levels of viral divergence were observed in the CNS than the lung after intranasal challenge with a high frequency of mutations in the spike Furin cleavage site (FCS). Deletion of the FCS significantly attenuated virulence after intranasal challenge, with lower viral titres and decreased morbidity compared with the wild-type virus. Intracranial inoculation of the FCS-deleted virus, however, was sufficient to restore virulence. After intracranial inoculation, both viruses established Infection in the lung, but dissemination from the CNS to the lung required the intact FCS. Cumulatively, these data suggest a critical role for the FCS in determining SARS-CoV-2 tropism and compartmentalization.

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