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J Virol, May 1998, p. 4127-4138, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Bovine Viral Diarrhea Virus Strain Oregon: a Novel Mechanism for Processing of NS2-3 Based on Point Mutations

Beate M. Kümmerer,1 Dieter Stoll,2 and Gregor Meyers1,*

Department of Clinical Virology, Federal Research Centre for Virus Diseases of Animals, D-72076 Tübingen,1 and NMI, D-72762 Reutlingen,2 Germany

Received 10 November 1997/Accepted 20 January 1998

Bovine viral diarrhea virus (BVDV) isolates can either be cytopathogenic (cp) or noncytopathogenic (noncp). While both biotypes express the nonstructural protein NS2-3, generation of NS3 strictly correlates with the cp phenotype. The production of NS3 is usually caused by cp specific genome alterations, which were found to be due to RNA recombination. Molecular analyses of the cp BVDV strain Oregon revealed that it does not possess such genome alterations but nevertheless is able to generate NS3 via processing of NS2-3. The NS3 serine protease is not involved in this cleavage, which, according to protein sequencing, occurs between amino acids 1589 and 1590 of the BVDV Oregon polyprotein. Transient-expression studies indicated that important information for the cleavage of NS2-3 is located within NS2. This was verified by expression of chimeric constructs containing cDNA fragments derived from BVDV Oregon and a noncp BVDV. It could be shown that the C-terminal part of NS2 plays a crucial role in NS2-3 cleavage. These data, together with results obtained by site-specific exchanges in this region, revealed a new mechanism for NS2-3 processing which is based on point mutations within NS2.

* Corresponding author. Mailing address: Department of Clinical Virology, Federal Research Centre for Virus Diseases of Animals, P.O. Box 1149, D-72001 Tübingen, Germany. Phone: 49 7071-967207. Fax: 49 7071-967303. E-mail: gregor.meyers{at}tue.bfav.de.

J Virol, May 1998, p. 4127-4138, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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