Canine parvovirus NS1 induces host translation shutoff by reducing mTOR phosphorylation.

Abstract

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 eIFα 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.

Importance: Autonomous parvoviruses, which possess compact genomes, are obligate intracellular parasites that necessitate host cell division for their replication cycle. Consequently, the modulation of host translation and usurpation of cellular machinery are hypothesized to facilitate immune evasion, enhance viral transmission, and perpetuate long-term infection. Despite the biological significance, the precise mechanisms by which autonomous parvoviruses regulate host translation remain understudied. Our study elucidates that CPV-2 infection induces a shutoff of host translation through the attenuation of mTOR phosphorylation. This mechanism may enable the virus to subvert the host immune response and engender pathogenic effects.