N(pro) of classical swine fever virus is an antagonist of double-stranded RNA-mediated apoptosis and IFN-alpha/beta induction.
Classical swine fever virus (CSFV) protects cells from double-stranded (ds) RNA-mediated apoptosis and IFN-alpha/beta induction. This phenotype is lost when CSFV lacks N(pro) (DeltaN(pro) CSFV). In the present study, we demonstrate that N(pro) counteracts dsRNA-mediated apoptosis and IFN-alpha/beta induction independently of other CSFV elements. For this purpose, we generated porcine SK-6 and PK-15 cell lines constitutively expressing N(pro) fused to the enhanced green fluorescent protein (EGFP). The survival of the SK6-EGFP-N(pro) cell line after polyinosinic polycytidylic acid [poly(IC)] treatment was comparable to that of CSFV-infected SK-6 cells and was significantly higher than the survival of the parent cell line. In PK-15 cells, the presence of EGFP-N(pro) prevented the DeltaN(pro) CSFV- and poly(IC)-mediated IFN-alpha/beta production. Importantly, N(pro) also inhibited IFN-alpha and IFN-beta promoter-driven luciferase expression in human cells and blocked IFN-alpha/beta induction mediated by Newcastle disease virus. This establishes a novel function for N(pro) in counteraction of the IFN-alpha/beta induction pathway.
Ruggli
Nicolas
N
Institute of Virology and Immunoprophylaxis (IVI), Mittelhäusern, Switzerland. nicolas.ruggli@ivi.admin.ch
Bird
Brian H
BH
Liu
Luzia
L
Bauhofer
Oliver
O
Tratschin
Jon-Duri
JD
Hofmann
Martin A
MA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006692:Classical Swine Fever Virus / Q000502:physiology*; D017931:DNA Primers; D010450:Endopeptidases / Q000494:pharmacology*; D017930:Genes, Reporter; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis*; D016899:Interferon-beta / Q000096:biosynthesis*; D007668:Kidney; D010957:Plasmids; D011070:Poly I-C / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000494:pharmacology; D014764:Viral Proteins / Q000494:pharmacology*
D017931:DNA Primers; D016898:Interferon-alpha; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins; D016899:Interferon-beta; D010450:Endopeptidases; C505229:N(pro) protein, swine fever virus; D011070:Poly I-C