Porcine reproductive and respiratory syndrome virus non-structural protein 1 suppresses tumor necrosis factor-alpha promoter activation by inhibiting NF-κB and Sp1

Sakthivel Subramaniam, Byungjoon Kwon, Lalit K. Beura, Charles A. Kuszynski, Asit K. Pattnaik, Fernando A. Osorio

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)270-279
Number of pages10
JournalVirology
Volume406
Issue number2
DOIs
StatePublished - Oct 2010

Keywords

  • Innate immune evasion
  • NF-κB
  • PRRSV
  • Promoter suppression
  • Sp1
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Virology

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