Canine parvovirus NS1 induces host translation shutoff by reducing mTOR phosphorylation

Canine parvovirus type 2 (CPV-2) is a member of the Parvoviridae family, characterized by its small, non-enveloped virions containing a linear single-stranded DNA genome of approximately 5 kb. Parvoviruses entirely reliant on the host cell's division machinery for replication. In this study, we demonstrate that CPV-2 infection triggers the host translation shutoff, a process in which the nonstructural protein 1 (NS1) plays a pivotal role. Our findings indicate that the CPV-2 NS1-induced host translation shutoff is not associated with transcription, protein degradation pathways, or eIF alpha phosphorylation, but rather involves the reduction of phosphorylation of the mammalian target of rapamycin (mTOR). In conclusion, this research reveals that CPV-2 NS1 induces a host translation shutoff by reducing mTOR phosphorylation, a mechanism that could potentially inform the development of more efficacious control and therapeutic strategies for CPV-2 and other parvoviral infections.