Classical swine fever virus interferes with cellular antiviral defense: evidence for a novel function of N(pro).
Classical swine fever virus (CSFV) replicates efficiently in cell lines and monocytic cells, including macrophages (MPhi), without causing a cytopathic effect or inducing interferon (IFN) secretion. In the present study, the capacity of CSFV to interfere with cellular antiviral activity was investigated. When the porcine kidney cell line SK-6 was infected with CSFV, there was a 100-fold increased capacity to resist to apoptosis induced by polyinosinic-polycytidylic acid [poly(IC)], a synthetic double-stranded RNA. In MPhi, the virus infection inhibited poly(IC)-induced alpha/beta IFN (type I IFN) synthesis. This interference with cellular antiviral defense correlated with the presence of the viral N(pro) gene. Mutants lacking the N(pro) gene (DeltaN(pro) CSFV) did not protect SK-6 cells from poly(IC)-induced apoptosis, despite growth properties and protein expression levels similar to those of the wild-type virus. Furthermore, DeltaN(pro) CSFV did not prevent poly(IC)-induced type I IFN production in MPhi but rather induced type I IFN in the absence of poly(IC) in both MPhi and the porcine kidney cell line PK-15, but not in SK-6 cells. With MPhi and PK-15, an impaired replication of the DeltaN(pro) CSFV compared with wild-type virus was noted. In addition, DeltaN(pro) CSFV, but not wild-type CSFV, could interfere with vesicular stomatitis virus replication in PK-15 cells. Taken together, these results provide evidence for a novel function associated with CSFV N(pro) with respect to the inhibition of the cellular innate immune system.
Ruggli
Nicolas
N
Institute of Virology and Immunoprophylaxis, Mittelhäusern, Switzerland. nicolas.ruggli@ivi.admin.ch
Tratschin
Jon-Duri
JD
Schweizer
Matthias
M
McCullough
Kenneth C
KC
Hofmann
Martin A
MA
Summerfield
Artur
A
D000818:Animals; D000998:Antiviral Agents / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D006692:Classical Swine Fever Virus / Q000502:physiology*; D007150:Immunohistochemistry; D013552:Swine; D014779:Virus Replication
D000998:Antiviral Agents