Porcine reproductive and respiratory syndrome virus non-structural protein 1 suppresses tumor necrosis factor-alpha promoter activation by inhibiting NF-κB and Sp1.
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-κB(3) 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.
Subramaniam
Sakthivel
S
School of Veterinary Medicine & Biomedical Sciences, University of Nebraska-Lincoln, NE 68583, USA.
Kwon
Byungjoon
B
Beura
Lalit K
LK
Kuszynski
Charles A
CA
Pattnaik
Asit K
AK
Osorio
Fernando A
FA
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015536:Down-Regulation; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D019318:Porcine Reproductive and Respiratory Syndrome / Q000235:genetics* / Q000378:metabolism; D019316:Porcine respiratory and reproductive syndrome virus / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D013552:Swine; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*
D016328:NF-kappa B; D016329:Sp1 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D017361:Viral Nonstructural Proteins