tetano
Editor, Senior Moderator
Virology
. 2024 Jan 28:592:109997.
doi: 10.1016/j.virol.2024.109997. Online ahead of print. A cell-adapted SARS-CoV-2 mutant, showing a deletion in the spike protein spanning the furin cleavage site, has reduced virulence at the lung level in K18-hACE2 mice
Fabrizia Valleriani[SUP] 1 [/SUP], Chiara Di Pancrazio[SUP] 1 [/SUP], Massimo Spedicato[SUP] 1 [/SUP], Giovanni Di Teodoro[SUP] 1 [/SUP], Daniela Malatesta[SUP] 1 [/SUP], Tetyana Petrova[SUP] 1 [/SUP], Francesca Profeta[SUP] 1 [/SUP], Maria Loredana Colaianni[SUP] 2 [/SUP], Shadia Berjaoui[SUP] 1 [/SUP], Ilaria Puglia[SUP] 1 [/SUP], Marialuigia Caporale[SUP] 1 [/SUP], Emanuela Rossi[SUP] 1 [/SUP], Maurilia Marcacci[SUP] 1 [/SUP], Mirella Luciani[SUP] 1 [/SUP], Flavio Sacchini[SUP] 1 [/SUP], Ottavio Portanti[SUP] 1 [/SUP], Francesco Bencivenga[SUP] 3 [/SUP], Nicola Decaro[SUP] 4 [/SUP], Francesco Bonfante[SUP] 5 [/SUP], Alessio Lorusso[SUP] 6 [/SUP]
Affiliations
Here we investigated the virulence properties of a unique cell-adapted SARS-CoV-2 mutant showing a ten-amino acid deletion encompassing the furin cleavage site of the spike protein (Δ[SUB]680[/SUB]SPRAARSVAS[SUB]689[/SUB]; Δ680-689-B.1) in comparison to its parental strain (wt-B.1) and two Delta variants (AY.122 and AY.21) of concern. After intranasal inoculation, transgenic K18-hACE2 mice were monitored for 14 days for weight change, lethality, and clinical score; oral swabs were daily collected and tested for the presence of N protein subgenomic RNA. At 3 and 7 dpi mice were also sacrificed and organs collected for molecular, histopathological, and immune response profile investigations. The Δ680-689-B.1-infected mice exhibited reduced shedding, lower virulence at the lung level, and milder pulmonary lesions. In the lung, infection with Δ680-689-B.1 was associated with a significant lower expression of some cytokines at 3 dpi (IL-4, IL-27, and IL-28) and 7 dpi (IL-4, IL-27, IL-28, IFN-γ and IL-1α).
Keywords: Deletion; Furin cleavage site; K18-hACE2 mice; SARS-CoV-2; Spike protein.
. 2024 Jan 28:592:109997.
doi: 10.1016/j.virol.2024.109997. Online ahead of print. A cell-adapted SARS-CoV-2 mutant, showing a deletion in the spike protein spanning the furin cleavage site, has reduced virulence at the lung level in K18-hACE2 mice
Fabrizia Valleriani[SUP] 1 [/SUP], Chiara Di Pancrazio[SUP] 1 [/SUP], Massimo Spedicato[SUP] 1 [/SUP], Giovanni Di Teodoro[SUP] 1 [/SUP], Daniela Malatesta[SUP] 1 [/SUP], Tetyana Petrova[SUP] 1 [/SUP], Francesca Profeta[SUP] 1 [/SUP], Maria Loredana Colaianni[SUP] 2 [/SUP], Shadia Berjaoui[SUP] 1 [/SUP], Ilaria Puglia[SUP] 1 [/SUP], Marialuigia Caporale[SUP] 1 [/SUP], Emanuela Rossi[SUP] 1 [/SUP], Maurilia Marcacci[SUP] 1 [/SUP], Mirella Luciani[SUP] 1 [/SUP], Flavio Sacchini[SUP] 1 [/SUP], Ottavio Portanti[SUP] 1 [/SUP], Francesco Bencivenga[SUP] 3 [/SUP], Nicola Decaro[SUP] 4 [/SUP], Francesco Bonfante[SUP] 5 [/SUP], Alessio Lorusso[SUP] 6 [/SUP]
Affiliations
- PMID: 38324940
- DOI: 10.1016/j.virol.2024.109997
Here we investigated the virulence properties of a unique cell-adapted SARS-CoV-2 mutant showing a ten-amino acid deletion encompassing the furin cleavage site of the spike protein (Δ[SUB]680[/SUB]SPRAARSVAS[SUB]689[/SUB]; Δ680-689-B.1) in comparison to its parental strain (wt-B.1) and two Delta variants (AY.122 and AY.21) of concern. After intranasal inoculation, transgenic K18-hACE2 mice were monitored for 14 days for weight change, lethality, and clinical score; oral swabs were daily collected and tested for the presence of N protein subgenomic RNA. At 3 and 7 dpi mice were also sacrificed and organs collected for molecular, histopathological, and immune response profile investigations. The Δ680-689-B.1-infected mice exhibited reduced shedding, lower virulence at the lung level, and milder pulmonary lesions. In the lung, infection with Δ680-689-B.1 was associated with a significant lower expression of some cytokines at 3 dpi (IL-4, IL-27, and IL-28) and 7 dpi (IL-4, IL-27, IL-28, IFN-γ and IL-1α).
Keywords: Deletion; Furin cleavage site; K18-hACE2 mice; SARS-CoV-2; Spike protein.