CYTOPATHOGENICITY OF A PESTIVIRUS CORRELATES WITH A 27-NUCLEOTIDE INSERTION

Cytopathogenic (cp) bovine viral diarrhea virus (BVDV) strains are gen erated in cattle persistently infected with noncytopathogenic (noncp) BVDV. cp BVDV strains are considered crucial for the development of fa tal mucosal disease. Comparative analysis of cp and noncp BVDV strains isolated from one animal suffering from mucosal disease revealed that the genomes of the cp BVDV strain (CP7) and the corresponding noncp B VDV strain (NCP7) are highly homologous. However, only the genome of C P7 contains an insertion of 27 nucleotides in the NS2 coding region. T he inserted sequence represents a duplication of bases 4064 to 4090 of the viral genome, located between the formerly neighboring nucleotide s 4353 and 4354. Parts of the viral polyproteins of CP7 and NCP7 were expressed in the T7 vaccinia virus system. These studies revealed that the insertion identified in the CP7 genome is necessary and sufficien t for the induction of NS2-3 cleavage. Since the expression of NS3 is strictly correlated to cp BVDV, the insertion identified in the genome of BVDV CP7 represents most likely the relevant mutation leading to t he evolvement of CP7 from NCP7.