The Npro product of classical swine fever virus and bovine viral diarrhea virus uses a conserved mechanism to target interferon regulatory factor-3.
Classical swine fever virus (CSFV) is a member of the genus Pestivirus in the family Flaviviridae. The N(pro) product of CSFV targets the host's innate immune response and can prevent the production of type I interferon (IFN). The mechanism by which CSFV orchestrates this inhibition was investigated and it is shown that, like the related pestivirus bovine viral diarrhea virus (BVDV), this involves the N(pro) protein targeting interferon regulatory factor-3 (IRF-3) for degradation by proteasomes and thus preventing IRF-3 from activating transcription from the IFN-beta promoter. Like BVDV, the steady-state levels of IRF-3 mRNA are not reduced markedly by CSFV infection or N(pro) overexpression. Moreover, IFN-alpha stimulation of CSFV-infected cells induces the antiviral protein MxA, indicating that, as in BVDV-infected cells, the JAK/STAT pathway is not targeted for inhibition.
Seago
Julian
J
Institute for Animal Health, Pirbright Laboratory, Ash Road, Pirbright, Surrey GU24 0NF, UK.
Hilton
Louise
L
Division of Basic Medical Sciences, St George's, University of London, London SW17 0RE, UK.
Reid
Elizabeth
E
Institute for Animal Health, Pirbright Laboratory, Ash Road, Pirbright, Surrey GU24 0NF, UK.
Doceul
Virginie
V
Institute for Animal Health, Pirbright Laboratory, Ash Road, Pirbright, Surrey GU24 0NF, UK.
Jeyatheesan
Janan
J
Division of Basic Medical Sciences, St George's, University of London, London SW17 0RE, UK.
Moganeradj
Kartykayan
K
Division of Basic Medical Sciences, St George's, University of London, London SW17 0RE, UK.
McCauley
John
J
Institute for Animal Health, Compton Laboratory, Compton, Newbury, Berkshire RG20 7NN, UK.
Charleston
Bryan
B
Institute for Animal Health, Pirbright Laboratory, Ash Road, Pirbright, Surrey GU24 0NF, UK.
Goodbourn
Stephen
S
Division of Basic Medical Sciences, St George's, University of London, London SW17 0RE, UK.
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D006692:Classical Swine Fever Virus / Q000276:immunology*; D010450:Endopeptidases / Q000276:immunology*; D050838:Interferon Regulatory Factor-3 / Q000037:antagonists & inhibitors* / Q000276:immunology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D013552:Swine; D014764:Viral Proteins / Q000276:immunology*
D050838:Interferon Regulatory Factor-3; C507353:Npro protein, bovine viral diarrhea virus; D014764:Viral Proteins; D010450:Endopeptidases; C505229:N(pro) protein, swine fever virus; D046988:Proteasome Endopeptidase Complex