A defective viral genome strategy elicits broad protective immunity against respiratory viruses

RNA viruses generate defective viral genomes (DVGs) that can interfere with replication of the parental wild type virus. To examine their therapeutic potential, we created a DVG by deleting the capsid-coding region of poliovirus. Strikingly, intraperitoneal or intranasal administration of this genome, which we termed eTIP1, elicits an antiviral response, inhibits replication, and protects mice from several RNA viruses, including enteroviruses, influenza, and SARS-CoV-2. While eTIP1 replication following intranasal administration is limited to the nasal cavity, its antiviral action extends non-cell-autonomously to the lungs. eTIP1 broad-spectrum antiviral effects are mediated by both local and distal type I interferon responses. Importantly, while a single eTIP1 dose protects animals from SARS-CoV-2 infection, it also stimulates production of SARS-CoV-2 neutralizing antibodies that afford long-lasting protection from SARS-CoV-2 reinfection. Thus, eTIP1 is a safe and effective broad-spectrum antiviral generating short-and long-term protection against SARSCoV-2 and other respiratory infections in animal models.

Automated summary

Researchers created an antiviral genome eTIP1 by deleting the capsid-coding region of poliovirus, showing significant therapeutic effects against RNA viruses. eTIP1 not only limits virus replication in the nasal cavity but also exerts a non-cell-autonomous antiviral action in the lungs through inducing interferon responses. Moreover, a single dose of eTIP1 not only protects animals from SARS-CoV-2 infection, but also stimulates antibody production for long-term protection.