Bvdv Genomic Organization and Proteins

BVDV, currently classified in the pestivirus genus of the family Flaviviridae, are small, enveloped viruses having a single-stranded positive-sense RNA genome. The BVDV genome is approximately 12.3 kb in length with a 5'-nontranslated region (NTR), a single large open reading frame (ORF), and a 3'-NTR lacking a poly(A)tail. The 5'-NTR contains an internal ribosome entry site that initiates translation of BVDV mRNA in a cap-independent manner. The secondary structure of the 5'-NTR is involved in the regulation of both translation and genome replication. The ORF is translated into a single polyprotein of approximately 4000 amino acids that is co-and post-translationally cleaved into 11 or 12 mature proteins by viral and host proteases. The order of proteins in the polyprotein is Npro (a nonstructural autoprotease unique to pestiviruses), the capsid protein (C), the envelope glycoproteins (Erns, E1, and E2), and the nonstructural proteins (p7, NS2/NS3, NS4A, NS4B, NS5A, and NS5B). NS3 (NS2/NS3) has helicase, serine protease, and NTPase activities, and NS5A has RNA-dependent RNA-polymerase activity. The NS2/NS3 complex is not cleaved in BVDV isolates that are noncytopathic in cell culture, while in isolates that are cytopathic both NS2/NS3 and a discrete NS3 are observed. The processing of NS2/NS3 appears to develop from RNA recombination events during the genomic replication of a noncytopathic virus. As a result, the genome of cytopathic isolates may contain genomic duplications, deletions, rearrangements, and/or insertions of cellular mRNA.