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Journal of Virology, July 2003, p. 7645-7654, Vol. 77, No. 13
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.13.7645-7654.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Classical Swine Fever Virus Interferes with Cellular Antiviral Defense: Evidence for a Novel Function of Npro

Nicolas Ruggli,1* Jon-Duri Tratschin,1 Matthias Schweizer,2 Kenneth C. McCullough,1 Martin A. Hofmann,1 and Artur Summerfield1

Institute of Virology and Immunoprophylaxis, Mittelhäusern,1 Institute of Veterinary Virology, University of Berne, Switzerland2

Received 15 October 2002/ Accepted 1 April 2003

Classical swine fever virus (CSFV) replicates efficiently in cell lines and monocytic cells, including macrophages (M{Phi}), 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 M{Phi}, 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 Npro gene. Mutants lacking the Npro gene ({Delta}Npro 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, {Delta}Npro CSFV did not prevent poly(IC)-induced type I IFN production in M{Phi} but rather induced type I IFN in the absence of poly(IC) in both M{Phi} and the porcine kidney cell line PK-15, but not in SK-6 cells. With M{Phi} and PK-15, an impaired replication of the {Delta}Npro CSFV compared with wild-type virus was noted. In addition, {Delta}Npro 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 Npro with respect to the inhibition of the cellular innate immune system.

* Corresponding author. Mailing address: Institute of Virology and Immunoprophylaxis (IVI), Sensemattstrasse 293, CH-3147 Mittelhäusern, Switzerland. Phone: 41 31 848 9211. Fax: 41 31 848 9222. E-mail: nicolas.ruggli{at}ivi.admin.ch.

Journal of Virology, July 2003, p. 7645-7654, Vol. 77, No. 13
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.13.7645-7654.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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