tetano
Editor, Senior Moderator
Nat Microbiol
. 2024 Aug 23.
doi: 10.1038/s41564-024-01786-8. Online ahead of print. Evolution of SARS-CoV-2 in the murine central nervous system drives viral diversification
Jacob Class[SUP] #[/SUP][SUP] 1 [/SUP], Lacy M Simons[SUP] #[/SUP][SUP] 2 3 [/SUP], Ramon Lorenzo-Redondo[SUP] 2 3 [/SUP], Jazmin Galván Achi[SUP] 1 [/SUP], Laura Cooper[SUP] 1 [/SUP], Tanushree Dangi[SUP] 4 [/SUP], Pablo Penaloza-MacMaster[SUP] 4 [/SUP], Egon A Ozer[SUP] 2 3 [/SUP], Sarah E Lutz[SUP] 5 [/SUP], Lijun Rong[SUP] 1 [/SUP], Judd F Hultquist[SUP] 6 7 [/SUP], Justin M Richner[SUP] 8 [/SUP]
Affiliations
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.
. 2024 Aug 23.
doi: 10.1038/s41564-024-01786-8. Online ahead of print. Evolution of SARS-CoV-2 in the murine central nervous system drives viral diversification
Jacob Class[SUP] #[/SUP][SUP] 1 [/SUP], Lacy M Simons[SUP] #[/SUP][SUP] 2 3 [/SUP], Ramon Lorenzo-Redondo[SUP] 2 3 [/SUP], Jazmin Galván Achi[SUP] 1 [/SUP], Laura Cooper[SUP] 1 [/SUP], Tanushree Dangi[SUP] 4 [/SUP], Pablo Penaloza-MacMaster[SUP] 4 [/SUP], Egon A Ozer[SUP] 2 3 [/SUP], Sarah E Lutz[SUP] 5 [/SUP], Lijun Rong[SUP] 1 [/SUP], Judd F Hultquist[SUP] 6 7 [/SUP], Justin M Richner[SUP] 8 [/SUP]
Affiliations
- PMID: 39179693
- DOI: 10.1038/s41564-024-01786-8
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.