PMID: 9188600Jul 1, 1997Paper

Bovine viral diarrhea virus NS3 serine proteinase: polyprotein cleavage sites, cofactor requirements, and molecular model of an enzyme essential for pestivirus replication

Journal of Virology
J XuC M Rice

Abstract

Members of the Flaviviridae encode a serine proteinase termed NS3 that is responsible for processing at several sites in the viral polyproteins. In this report, we show that the NS3 proteinase of the pestivirus bovine viral diarrhea virus (BVDV) (NADL strain) is required for processing at nonstructural (NS) protein sites 3/4A, 4A/4B, 4B/5A, and 5A/5B but not for cleavage at the junction between NS2 and NS3. Cleavage sites of the proteinase were determined by amino-terminal sequence analysis of the NS4A, NS4B, NS5A, and NS5B proteins. A conserved leucine residue is found at the P1 position of all four cleavage sites, followed by either serine (3/4A, 4B/5A, and 5A/5B sites) or alanine (4A/4B site) at the P1' position. Consistent with this cleavage site preference, a structural model of the pestivirus NS3 proteinase predicts a highly hydrophobic P1 specificity pocket. trans-Processing experiments implicate the 64-residue NS4A protein as an NS3 proteinase cofactor required for cleavage at the 4B/5A and 5A/5B sites. Finally, using a full-length functional BVDV cDNA clone, we demonstrate that a catalytically active NS3 serine proteinase is essential for pestivirus replication.

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Citations

Sep 13, 2007·The Journal of Biological Chemistry·Birke Andrea Tews, Gregor Meyers
Mar 23, 2012·Journal of Veterinary Science·Gil-Soon ParkJae-Young Song
Mar 30, 2012·PLoS Pathogens·Christiane RiedelTillmann Rümenapf
Jul 10, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·D MoradpourH E Blum
May 28, 2003·Journal of Virology·Jin-Hua SunMin Gao
Feb 26, 2005·Journal of Virology·Young-Min LeeCharles M Rice
Apr 3, 2007·Protein Science : a Publication of the Protein Society·Alexander E AleshinRobert C Liddington
Feb 14, 2004·Journal of Virology·Eugene V AgapovCharles M Rice
Jan 29, 2011·Journal of Virology·Benjamin LampTillmann Rümenapf
Jun 9, 2015·Animal Health Research Reviews·Martin BeerSandra Blome
Aug 25, 2017·Journal of Virology·Fengwei ZhengZishu Pan
Jan 23, 2010·The Journal of Biological Chemistry·Ioana Bintintan, Gregor Meyers
Apr 13, 2013·The Journal of General Virology·Peter Christian RisagerGraham J Belsham

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