E3 ligase ASB8 promotes porcine reproductive and respiratory syndrome virus proliferation by stabilizing the viral Nsp1 α protein and degrading host IKKβ kinase.

In this study, we demonstrated that PRRSV Nsp1α interacted with the host E3 ubiquitin ligase ankyrin repeat and SOCS box-containing 8 (ASB8). Specifically, porcine ASB8 promoted K63-linked ubiquitination and increased stability of Nsp1α and boosted PRRSV replication. Moreover, we found that ASB8 was phosphorylated at the N-terminal Ser-31 by host IκB kinase β (IKKβ). In turn, ASB8 facilitated K48-linked ubiquitination and degradation of IKKβ via the ubiquitin-proteasome pathway, resulting in remarkable inhibition of I-kappa-B-alpha (IκBα) and of p65 phosphorylation, consequently suppressing NF-κB activity. Our results provide evidence that PRRSV Nsp1α hijacks up-regulated host ASB8 to escape from intrinsic antiviral immunity. PMID: 31009856 [PubMed - as supplied by publisher]
Source: Virology - Category: Virology Authors: Tags: Virology Source Type: research