tetano
Editor, Senior Moderator
Front Immunol
. 2024 Nov 27:15:1501200.
doi: 10.3389/fimmu.2024.1501200. eCollection 2024. Single spike mutation differentiating XBB.1 and XBB.1.5 enhances SARS-CoV-2 cell-to-cell transmission and facilitates serum-mediated enhancement
Elena Criscuolo[SUP] #[/SUP][SUP] 1 [/SUP], Benedetta Giuliani[SUP] #[/SUP][SUP] 1 [/SUP], Matteo Castelli[SUP] 1 [/SUP], Mattia Cavallaro[SUP] 1 [/SUP], Sofia Sisti[SUP] 1 [/SUP], Roberto Burioni[SUP] 1 [/SUP], Davide Ferrari[SUP] 2 [/SUP], Nicasio Mancini[SUP] 3 [/SUP], Massimo Locatelli[SUP] 4 [/SUP], Nicola Clementi[SUP] 1 4 [/SUP]
Affiliations
Introduction: The ongoing emergence of SARS-CoV-2 variants poses significant challenges to existing therapeutics. The spike (S) glycoprotein is central to both viral entry and cell-to-cell transmission via syncytia formation, a process that confers resistance to neutralizing antibodies. The mechanisms underlying this resistance, particularly in relation to spike-mediated fusion, remain poorly understood.
Methods: We analyzed two clinical SARS-CoV-2 isolates differing by a single amino acid substitution in the S protein. Using biochemical and cell-based assays, we evaluated entry kinetics, syncytia formation, and the neutralizing efficacy of convalescent sera. These parameters were further correlated with S-mediated cell-cell fusion activity.
Results: The single amino acid substitution significantly altered entry kinetics and enhanced syncytia formation. This modification did not diminished the neutralizing capacity of convalescent sera, but it increased the efficiency of S-induced cell-cell fusion. These findings highlight the mutation's impact on viral transmissibility and immune evasion.
Discussion: Our study demonstrates that even minor changes in the S protein can profoundly influence SARS-CoV-2 transmissibility and resistance to antibody-mediated neutralization. Understanding the molecular basis of S-mediated cell-cell fusion is crucial for anticipating the impact of emerging variants and developing next-generation therapeutic strategies. These insights provide a framework for predicting variant fitness and optimizing treatment approaches against future SARS-CoV-2 variants.
Keywords: COVID-19; SARS-CoV-2; Spike; XBB.1; XBB.1.5; fusion; neutralizing antibodies.
. 2024 Nov 27:15:1501200.
doi: 10.3389/fimmu.2024.1501200. eCollection 2024. Single spike mutation differentiating XBB.1 and XBB.1.5 enhances SARS-CoV-2 cell-to-cell transmission and facilitates serum-mediated enhancement
Elena Criscuolo[SUP] #[/SUP][SUP] 1 [/SUP], Benedetta Giuliani[SUP] #[/SUP][SUP] 1 [/SUP], Matteo Castelli[SUP] 1 [/SUP], Mattia Cavallaro[SUP] 1 [/SUP], Sofia Sisti[SUP] 1 [/SUP], Roberto Burioni[SUP] 1 [/SUP], Davide Ferrari[SUP] 2 [/SUP], Nicasio Mancini[SUP] 3 [/SUP], Massimo Locatelli[SUP] 4 [/SUP], Nicola Clementi[SUP] 1 4 [/SUP]
Affiliations
- PMID: 39664381
- PMCID: PMC11631925
- DOI: 10.3389/fimmu.2024.1501200
Introduction: The ongoing emergence of SARS-CoV-2 variants poses significant challenges to existing therapeutics. The spike (S) glycoprotein is central to both viral entry and cell-to-cell transmission via syncytia formation, a process that confers resistance to neutralizing antibodies. The mechanisms underlying this resistance, particularly in relation to spike-mediated fusion, remain poorly understood.
Methods: We analyzed two clinical SARS-CoV-2 isolates differing by a single amino acid substitution in the S protein. Using biochemical and cell-based assays, we evaluated entry kinetics, syncytia formation, and the neutralizing efficacy of convalescent sera. These parameters were further correlated with S-mediated cell-cell fusion activity.
Results: The single amino acid substitution significantly altered entry kinetics and enhanced syncytia formation. This modification did not diminished the neutralizing capacity of convalescent sera, but it increased the efficiency of S-induced cell-cell fusion. These findings highlight the mutation's impact on viral transmissibility and immune evasion.
Discussion: Our study demonstrates that even minor changes in the S protein can profoundly influence SARS-CoV-2 transmissibility and resistance to antibody-mediated neutralization. Understanding the molecular basis of S-mediated cell-cell fusion is crucial for anticipating the impact of emerging variants and developing next-generation therapeutic strategies. These insights provide a framework for predicting variant fitness and optimizing treatment approaches against future SARS-CoV-2 variants.
Keywords: COVID-19; SARS-CoV-2; Spike; XBB.1; XBB.1.5; fusion; neutralizing antibodies.