Graduate Student Expo 2011
Yan Sun, PhD candidate
The inhibition function of Type I interferon by Nsp 11 from PRRSV
Advisor: D. Yoo
Type I IFN plays a key role in antiviral activities and PRRSV has been shown to down-regulate IFN response in both virus infected cells and pigs. In this study, we showed Nsp11 contained a strong suppressive activity for IFN-β production. Nsp11 suppressed both IRF3 and NF-kB activities at cell cytoplasm when stimulated with dsRNA analogue or TNFα. Nsp11 inhibited the phosphorylation of both IRF3 and IkB and as a consequence, IRF3 and NF-kB nuclear translocation was blocked, leading to the inhibition of IFN production pathways. This inhibition was through RIG-I mediated signaling pathway and IPS-1, a common component during both IRF3 and NF-kB activation, was degraded in both Nsp11-expressing and PRRSV-infected cells. Since Nsp11 is a nidovirus specific endoribonuclease, the structure function relationship studies were conducted using a series of Nsp11 mutants for their abilities for IFN regulation. Mutants that impaired the NendoU activity lost the IFN inhibitory activity, and the degradation of IPS-1 was blocked. Taken together, the data suggest that Nsp11 functions as an IFN antagonist and its NendoU activity plays an important role for virus replication and IFN suppression.