E3 ligase ASB8 promotes porcine reproductive and respiratory syndrome virus proliferation by stabilizing the viral Nsp1α protein and degrading host IKKβ kinase.

Porcine reproductive and respiratory syndrome virus (PRRSV) can potently suppress type I interferon production and escape from innate immune responses. PRRSV nonstructural protein 1α (Nsp1α) can inhibit IFN-β and NF-κB gene promoter activities, but the precise mechanisms are largely unclear. 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.