The objective of this study was to identify porcine reproductive and respiratory syndrome virus (PRRSV)-encoded proteins that are responsible for the inhibition of TNF-α expression and the mechanism(s) involved in this phenomenon. Using a TNF-α promoter reporter system, the non-structural protein 1 (Nsp1) was found to strongly suppress the TNF-α promoter activity. Such inhibition takes place especially at the promoter's proximal region. Both Nsp1α and Nsp1β, the two proteolytic fragments of Nsp1, were shown to be involved in TNF-α promoter suppression. Furthermore, using reporter plasmids specific for transcription factors (TFs) that bind to TNF-α promoter, Nsp1α and Nsp1β were demonstrated to inhibit the activity of the TFs that bind CRE-κB3 and Sp1 elements respectively. Subsequent analyses showed that Nsp1α moderately inhibits NF-κB activation and that Nsp1β completely abrogates the Sp1 transactivation. These findings reveal one of the important mechanisms underlying the innate immune evasion by PRRSV during infection.
Bibliographical noteFunding Information:
In order to prepare primary cells ex vivo , blood was collected from donor pigs by following protocols approved by the Institutional Animal Care and Use Committee of the University of Nebraska-Lincoln under the protocol IACUC No.07-10-048C. This research has been supported by a grant from the USDA NRICGP (project 2008-00903 USDA-NRICGP).
- Innate immune evasion
- Promoter suppression
- Tumor necrosis factor-α