tetano
Editor, Senior Moderator
Commun Biol
. 2025 Aug 30;8(1):1322.
doi: 10.1038/s42003-025-08768-4. Engineering virus-like particles for safe and versatile modeling of SARS-CoV-2 host interaction and immune escape
Liang Ma[SUP] #[/SUP][SUP] 1 2 [/SUP], Yuan Lin[SUP] #[/SUP][SUP] 3 [/SUP], Siyu Ma[SUP] 1 2 4 [/SUP], Kai Chen[SUP] 1 2 [/SUP], Yihan Lin[SUP] 5 6 7 [/SUP]
Affiliations
The continuous evolution of SARS-CoV-2 poses global health challenges. A safe, rapid, and versatile method for assessing functions of Spike protein mutations in ACE2 receptor binding and immune evasion would be highly valuable. To address this, we engineered a transcription- and replication-competent virus-like particle (trVLP) derived from the Sindbis virus, pseudotyped with the SARS-CoV-2 receptor binding domain (RBD). This trVLP exclusively propagates in BHK-21 cells engineered to express both RNA replicase and human ACE2, providing a controllable, safe model of SARS-CoV-2 RBD-ACE2 interaction-mediated virus entry. The system enables characterization of RBD interactions with ACE2 from various mammalian hosts, demonstrating its utility for studying host-virus interactions. By leveraging the evolutionary capability of trVLP mediated by error-prone RNA replication, we screened for RBD variants that evade the antibody-mediated inhibition of cell entry. Together, these findings underscore the utility of the trVLP as a safe, rapid, and flexible platform for dissecting SARS-CoV-2 RBD evolution and identifying key adaptive mutations with implications for surveillance and countermeasure development.
. 2025 Aug 30;8(1):1322.
doi: 10.1038/s42003-025-08768-4. Engineering virus-like particles for safe and versatile modeling of SARS-CoV-2 host interaction and immune escape
Liang Ma[SUP] #[/SUP][SUP] 1 2 [/SUP], Yuan Lin[SUP] #[/SUP][SUP] 3 [/SUP], Siyu Ma[SUP] 1 2 4 [/SUP], Kai Chen[SUP] 1 2 [/SUP], Yihan Lin[SUP] 5 6 7 [/SUP]
Affiliations
- PMID: 40885856
- PMCID: PMC12398559
- DOI: 10.1038/s42003-025-08768-4
The continuous evolution of SARS-CoV-2 poses global health challenges. A safe, rapid, and versatile method for assessing functions of Spike protein mutations in ACE2 receptor binding and immune evasion would be highly valuable. To address this, we engineered a transcription- and replication-competent virus-like particle (trVLP) derived from the Sindbis virus, pseudotyped with the SARS-CoV-2 receptor binding domain (RBD). This trVLP exclusively propagates in BHK-21 cells engineered to express both RNA replicase and human ACE2, providing a controllable, safe model of SARS-CoV-2 RBD-ACE2 interaction-mediated virus entry. The system enables characterization of RBD interactions with ACE2 from various mammalian hosts, demonstrating its utility for studying host-virus interactions. By leveraging the evolutionary capability of trVLP mediated by error-prone RNA replication, we screened for RBD variants that evade the antibody-mediated inhibition of cell entry. Together, these findings underscore the utility of the trVLP as a safe, rapid, and flexible platform for dissecting SARS-CoV-2 RBD evolution and identifying key adaptive mutations with implications for surveillance and countermeasure development.