Frontiers in Microbiology (Jul 2022)
Seneca Valley Virus 3Cpro Cleaves Heterogeneous Nuclear Ribonucleoprotein K to Facilitate Viral Replication
Abstract
Seneca Valley virus (SVV) has emerged as an important pathogen that is associated with idiopathic vesicular infection in pigs, causing a potential threat to the global swine industry. The heterogeneous nuclear ribonucleoprotein K (hnRNP K) that shuttles between the nucleus and cytoplasm plays an important role in viral infection. In this study, we observed that infection with SVV induced cleavage, degradation, and cytoplasmic redistribution of hnRNP K in cultured cells, which was dependent on the activity of viral 3Cpro protease. Also, the 3Cpro induced degradation of hnRNP K via the caspase pathway. Further studies demonstrated that SVV 3Cpro cleaved hnRNP K at residue Q364, and the expression of the cleavage fragment hnRNP K (aa.365–464) facilitates viral replication, which is similar to full-length hnRNP K, whereas hnRNP K (aa.1–364) inhibits viral replication. Additionally, hnRNP K interacts with the viral 5′ untranslated region (UTR), and small interfering RNA (siRNA)-mediated knockdown of hnRNP K results in significant inhibition of SVV replication. Overall, our results demonstrated that the hnRNP K positively regulates SVV replication in a protease activity-dependent fashion in which the cleaved C-terminal contributes crucially to the upregulation of SVV replication. This finding of the role of hnRNP K in promoting SVV propagation provides a novel antiviral strategy to utilize hnRNP K as a potential target for therapy.
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