摘要
Real-time sensing of viral infection in live cells is crucial for virology research and antiviral development.However,existing methods face challenges of low signal sensitivity and the necessity for viral manipulation and cell fixation.Here,we develop a Viral-Engineered RNA-based Activation System(VERAS)that harnesses the viral replicase to induce transgene expression upon viral infection.VERAS is designed to detect real-time viral tran-scription and replication in live cells,which can trigger the translation of reporter and therapeutic genes.By integrating a viral packaging sequence,VERAS can also be transmitted to neighboring cells through progeny virions,effectively acting as a'Trojan Horse'.The negative-stranded VERAS elements demonstrated effective detection of several coronaviruses,including 229E and OC43,due to the conservation of cis-acting RNA struc-tures across coronaviruses.Notably,VERAS functions as a dual-purpose system,acting both as an infection detector and inducible antiviral system.VERAS has the potential for basic virology research applications and can be adopted in improving the inducible expression of mRNA medicines for future coronaviruses.
基金
supported by a contract grant from Bill&Melinda Gates Foundation(INV-035661)and in part by funding to L.S.Q.as a Chan Zuckerberg Biohub-San Francisco Investigator
C.O.is supported by the National Science Foundation Graduate Research Fellowship Program(Grant DGE-2146755)
the Sarafan ChEM-H Chemistry-Biological Interface Training Program.
