title: Analysis of a pair of END+ and END- viruses derived from the same bovine viral diarrhea virus stock reveals the amino acid determinants in Npro responsible for inhibition of type I interferon production.
abstract: The Exaltation of Newcastle disease virus (END) phenomenon is induced by the inhibition of type I interferon in pestivirus-infected cells in vitro, via proteasomal degradation of cellular interferon regulatory factor (IRF)-3 with the property of the viral autoprotease protein N(pro). Reportedly, the amino acid residues in the zinc-binding TRASH motif of N(pro) determine the difference in characteristics between END-phenomenon-positive (END(+)) and END-phenomenon-negative (END(-)) classical swine fever viruses (CSFVs). However, the basic mechanism underlying this function in bovine viral diarrhea virus (BVDV) has not been elucidated from the genomic differences between END(+) and END(-) viruses using reverse genetics till date. In the present study, comparison of complete genome sequences of a pair of END(+) and END(-) viruses isolated from the same virus stock revealed that there were only four amino acid substitutions (D136G, I2623V, D3148G and D3502Y) between two viruses. Based on these differences, viruses with and without mutations at these positions were generated using reverse genetics. The END assay, measurements of induced type I interferon and IRF-3 detection in cells infected with these viruses revealed that the aspartic acid at position 136 in the zinc-binding TRASH motif of N(pro) was required to inhibit the production of type I interferon via the degradation of cellular IRF-3, consistently with CSFV.
authors: Food Safety and Consumer Affairs Bureau, Ministry of Agriculture, Forestry and Fisheries, Chiyoda-ku, Tokyo 100-8950, Japan.
authors: Takashi
authors: T
authors: Kozasa
authors: Yuri
authors: Y
authors: Abe
authors: Kazuya
authors: K
authors: Mitsuhashi
authors: Tomokazu
authors: T
authors: Tamura
authors: Hiroshi
authors: H
authors: Aoki
authors: Masatoshi
authors: M
authors: Ishimaru
authors: Shigeyuki
authors: S
authors: Nakamura
authors: Masatoshi
authors: M
authors: Okamatsu
authors: Hiroshi
authors: H
authors: Kida
authors: Yoshihiro
authors: Y
authors: Sakoda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003001:Cloning, Molecular; D001908:Diarrhea Viruses, Bovine Viral / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009154:Mutation; D013737:Testis / Q000166:cytology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D007370:Interferon Type I; C507353:Npro protein, bovine viral diarrhea virus; D014764:Viral Proteins
references: Jpn J Microbiol. 1968 Mar;12(1):35-49
references: 4970697
references: Am J Vet Res. 1970 Oct;31(10):1787-94
references: 4319263
references: Adv Virus Res. 1996;47:53-118
references: 8895831
references: J Virol. 1996 Jun;70(6):3478-87
references: 8648680
references: J Vet Med Sci. 1995 Aug;57(4):677-81
references: 8519897
references: Vet Microbiol. 1993 Dec;38(1-2):173-9
references: 8128599
references: J Virol. 1993 Dec;67(12):7088-95
references: 8230432
references: J Virol. 1993 Jun;67(6):3288-94
references: 8388499
references: Virology. 1988 Jul;165(1):200-8
references: 2838958
references: Vet Microbiol. 1987 Apr;13(4):383-7
references: 3037767
references: Infect Immun. 1976 Aug;14(2):332-6
references: 61176
references: J Virol. 1997 Jul;71(7):5415-22
references: 9188613
references: J Virol. 1998 Mar;72(3):2544-7
references: 9499122
references: In Vitro Cell Dev Biol Anim. 1998 Jan;34(1):53-7
references: 9542636
references: Science. 1958 Aug 15;128(3320):366
references: 13568799
references: J Virol. 2006 Jan;80(2):900-11
references: 16378992
references: Virus Res. 2006 Mar;116(1-2):78-84
references: 16216377
references: J Virol Methods. 2006 Dec;138(1-2):140-6
references: 17046073
references: J Virol. 2006 Dec;80(23):11723-32
references: 16971436
references: J Virol. 2007 Apr;81(7):3087-96
references: 17215286
references: Virology. 2007 Sep 30;366(2):277-92
references: 17531282
references: J Gen Virol. 2007 Nov;88(Pt 11):3002-6
references: 17947522
references: Virus Genes. 2008 Feb;36(1):135-9
references: 18181015
references: J Virol. 2009 Jan;83(2):817-29
references: 18987150
references: J Mol Biol. 2009 Aug 14;391(2):438-49
references: 19540847
references: J Vet Med Sci. 2014 Dec;76(12):1635-9
references: 25649948
references: J Virol. 2014 Jun;88(12):6983-92
references: 24719408
references: Vet Res. 2014;45:47
references: 24742209
references: PLoS Pathog. 2013;9(10):e1003704
references: 24146623
references: Arch Virol. 2013 Apr;158(4):753-63
references: 23178968
references: J Virol. 2012 Aug;86(16):8602-13
references: 22674973
references: Biologicals. 2011 Jul;39(4):242-8
references: 21719306
references: J Virol. 2011 Aug;85(16):8002-11
references: 21680532
references: Vet Microbiol. 2010 Apr 21;142(1-2):13-7
references: 19836906