The NPro product of bovine viral diarrhea virus inhibits DNA binding by interferon regulatory factor 3 and targets it for proteasomal degradation.
Bovine viral diarrhea virus (BVDV) is a pestivirus that can establish a persistent infection in the developing fetus and has the ability to disable the production of type I interferon. In this report, we extend our previous observations that BVDV encodes a protein able to specifically block the activity of interferon regulatory factor 3 (IRF-3), a transcription factor essential for interferon promoter activation, by demonstrating that this is a property of the N-terminal protease fragment (NPro) of the BVDV polyprotein. Although BVDV infections cause relocalization of cellular IRF-3 from the cytoplasm to the nucleus early in infection, NPro blocks IRF-3 from binding to DNA. NPro has the additional property of targeting IRF-3 for polyubiquitination and subsequent destruction by cellular multicatalytic proteasomes. The autoprotease activity of NPro is not required for the inhibition of type I interferon induction or the targeting of IRF-3 for degradation.
Hilton
Louise
L
Division of Basic Medical Sciences, St. George's, University of London, London SW17 0RE, United Kingdom.
Moganeradj
Kartykayan
K
Zhang
Gang
G
Chen
Yun-Hsiang
YH
Randall
Richard E
RE
McCauley
John W
JW
Goodbourn
Stephen
S
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D001908:Diarrhea Viruses, Bovine Viral / Q000472:pathogenicity / Q000502:physiology*; D050838:Interferon Regulatory Factor-3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D016899:Interferon-beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism* / Q000494:pharmacology
D004268:DNA-Binding Proteins; D050838:Interferon Regulatory Factor-3; D016898:Interferon-alpha; C507353:Npro protein, bovine viral diarrhea virus; D014764:Viral Proteins; D016899:Interferon-beta; D046988:Proteasome Endopeptidase Complex