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===Virus Structure===

===Virus Structure===

BVDV's RNA genome encodes both structural and non-structural proteins. These include ''Npro'', whose protease action generates the N-terminus of the protein ''C''. ''C'' protein packages genomic RNA and assists in the formation of the eventual enveloped virion. ''Erns'', ''E1'' and ''E2'' are all glycoproteins, with ''Erns'' possessing RNase activity involved in viral replication and pathogenesis⁵. ''E1'' is membrane-anchored and initiates the translocation of the antigenic protein ''E2'' to the envelope³. ''P7'' has an uncertain function⁶.

The BVDV genome comprises a single strand of positive sense RNA which is around 12.3 kilobases in length³. The genome is read in one 3898-codon open reading frame that contains no non-coding sequences. BVDV polyprotein is translated directly from the ORF and is cleaved by viral and cellular proteinases to form mature viral proteins^{3, 4}. At either end of the ORF, 5’ and 3’ untranslated regions exist. These regions are long, allowing them to accomodate fuctions conferred in eukaryotic DNA by the 5’ cap and the 3' poly-A tail, such as controlling the initiation of translation, facilitating the entry of replicases, and contributing to RNA stability⁴. BVDV's RNA genome encodes both structural and non-structural proteins. These include ''Npro'', whose protease action generates the N-terminus of the protein ''C''. ''C'' protein packages genomic RNA and assists in the formation of the eventual enveloped virion. ''Erns'', ''E1'' and ''E2'' are all glycoproteins, with ''Erns'' possessing RNase activity involved in viral replication and pathogenesis⁵. ''E1'' is membrane-anchored and initiates the translocation of the antigenic protein ''E2'' to the envelope³. ''P7'' has an uncertain function⁶. NS2-3 is the first non-structural protein to be translated. Sequence similarities are shown by NS2-3 to a region that in other Flaviviridae is split into two distinct polypeptides, NS2 and NS3. In BVDV, NS2 and NS3 can be expressed as separate polypeptides: NS3 is found exclusively in cytopathic isolates after 6 hours post-infection, making it an isolate of this biotype³. NS2 is also expressed as a discrete polypeptide in some, but not all, cytopathic isolates. NS2-3, along with the other non-structural proteins, plays an important role in genome replication. A serine protease domain within NS2-3 functions to release NS4A, NS4B, NS5A and NS5B⁷. NS4A is cofactor for the serine protease⁷, and NS5B possesses an RNA-dependent RNA polymerase activity⁸. Knowledge of the role of NS4B is limited.

 

NS2-3 is the first non-structural protein to be translated. Sequence similarities are shown by NS2-3 to a region that in other Flaviviridae is split into two distinct polypeptides, NS2 and NS3. In BVDV, NS2 and NS3 can be expressed as separate polypeptides: NS3 is found exclusively in cytopathic isolates after 6 hours post-infection, making it an isolate of this biotype³. NS2 is also expressed as a discrete polypeptide in some, but not all, cytopathic isolates.

 

The non-structural proteins play important roles in genome replication. The action of a serine protease domain within NS2-3 releases NS4A, NS4B, NS5A and NS5B (Harada et. al, 2000). NS4A goes on to act as a cofactor for the serine protease (Harada et. al, 2000), but knowledge of the role of NS4B is limited. NS5B possesses an RNA-dependent RNA polymerase activity (Zhong et. al, 1998). In the related Hepatitis C virus NS5B is an essential part of the replication complex (Brass et. al, 2006), and the function may be similar in BVDV.  

The structural proteins and the genomic material created by the actions of the non-stuctural proteins come together to form the 40-60nm BVDV virion. A central core of RNA packaged in the capsid protein (C), which is surrounded by a lipid membrane. The glycoproteins E1 and E2 are anchored within the membrane, and Erns is loosely associated. Since naked BVDV RNA is infectious (Dubovi, 1990; Donis, 1995), it is clear that virions do not contain RNA replication proteins. Instead, virion proteins and lipids “capture” the viral genome from the host cell cytoplasm and deliver it to that of uninfected cells. Enzymes for the production of new RNA from the genomic RNA template are provided by the infected host cell.

The structural proteins and the genomic material created by the actions of the non-stuctural proteins come together to form the 40-60nm BVDV virion. A central core of RNA packaged in the capsid protein (C), which is surrounded by a lipid membrane. The glycoproteins E1 and E2 are anchored within the membrane, and Erns is loosely associated. Since naked BVDV RNA is infectious (Dubovi, 1990; Donis, 1995), it is clear that virions do not contain RNA replication proteins. Instead, virion proteins and lipids “capture” the viral genome from the host cell cytoplasm and deliver it to that of uninfected cells. Enzymes for the production of new RNA from the genomic RNA template are provided by the infected host cell.