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==Bovine Viral Diarrhoea Virus==

==Bovine Viral Diarrhoea Virus==

===Classification===

===Classification===

The  viral aetiology of BVD was first established over 60 years ago, but it was not until the 1960s that the agent was assigned to the newly penned "Pestivirus" genus. At this stage Pestiviruses were considered to be non-arthropod-borne [[:Category:Togaviridae|Togaviruses]]; later, sequencing of genomic RNA showed that they are taxonomically better suited to the [[:Category:Flaviviridae|Flaviviridae]] family^{1, 2}. Many members of the Flaviviridae family are indeed arthropod-borne, such as the Flaviviruses [[West Nile Virus]] and Yellow Fever Virus. However, Pestiviruses are not transmitted by insects, and the genus includes pathogens of cattle (BVDV), sheep ([[Border Disease Virus]]) and pigs ([[Classical Swine Fever]] Virus).

The  viral aetiology of BVD was first established over 60 years ago, but it was not until the 1960s that the agent was assigned to the newly penned "Pestivirus" genus. At this stage Pestiviruses were considered to be non-arthropod-borne [[:Category:Togaviridae|Togaviruses]]; later, sequencing of genomic RNA showed that they are taxonomically better suited to the [[:Category:Flaviviridae|Flaviviridae]] family<ref name="one">Collett, M S et al (1988) '''Proteins encoded by bovine viral diarrhoea virus: The genomic organisation of a pestivirus.''' ''Virology'', 165(1), 200-208.</ref><ref name="two">Meyers, G et al (1989) '''Molecular Cloning and nucleotide sequence of the genome of hog cholera virus.''' ''Virology'', 171(2), 555-567.</ref>. Many members of the Flaviviridae family are indeed arthropod-borne, such as the Flaviviruses [[West Nile Virus]] and Yellow Fever Virus. However, Pestiviruses are not transmitted by insects, and the genus includes pathogens of cattle (BVDV), sheep ([[Border Disease Virus]]) and pigs ([[Classical Swine Fever]] Virus).

===Virus Structure===

===Virus Structure===

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 accomomdate functions 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 is the capsid protein that 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 from 6 hours post-infection, making it a marker of this biotype³. NS2 is also expressed as a discrete polypeptide in some 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 a cofactor for the serine protease⁷, and NS5B possesses an RNA-dependent RNA polymerase activity⁸. Knowledge of the role of NS4B is limited.

The BVDV genome comprises a single strand of positive sense RNA which is around 12.3 kilobases in length<ref name="three">Donis, R O(1995) '''Molecular biology of bovine viral diarrhea virus and its interactions with the host.''' ''The Veterinary Clinics of North America: Food Animal Practice'' 11(3), 393-424.</ref>. 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<ref name="three"/><ref name="four">Dubovi, E J (1990) '''Molecular biology of bovine virus diarrhoea virus.''' ''Revue Scientifique et Technique'', 9(1), 105-114.</ref>. At either end of the ORF, 5’ and 3’ untranslated regions exist. These regions are long, allowing them to accomomdate functions 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 stability<ref name="four"/>. 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 is the capsid protein that 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 pathogenesis<ref name="five">Van Gennip, H G P et al (2005) '''Dimerisation of glycoprotein Erns of classical swine fever virus is not essential for viral replication and infection.''' ''Archives of Virology'', 150(1), 2271-2286.</ref>. 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 from 6 hours post-infection, making it a marker of this biotype³. NS2 is also expressed as a discrete polypeptide in some 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 a cofactor for the serine protease⁷, and NS5B possesses an RNA-dependent RNA polymerase activity⁸. Knowledge of the role of NS4B is limited.

Newly formed genomic material is packaged by structural proteins to create the BVDV virion which is 40-60nm in diameter. The capsid is surrounded by a membranous envelope, in which the glycoproteins ''E1'' and ''E2'' are anchored. Naked BVDV RNA is infectious^{3, 4}, and so it can be deduced that the virions do not contain enzymes necessary for RNA replication: these are provided by the host cell.

Newly formed genomic material is packaged by structural proteins to create the BVDV virion which is 40-60nm in diameter. The capsid is surrounded by a membranous envelope, in which the glycoproteins ''E1'' and ''E2'' are anchored. Naked BVDV RNA is infectious^{3, 4}, and so it can be deduced that the virions do not contain enzymes necessary for RNA replication: these are provided by the host cell.

==References==

==References==

#Collett, M S et al (1988) '''Proteins encoded by bovine viral diarrhoea virus: The genomic organisation of a pestivirus.''' ''Virology'', 165(1), 200-208.

#Collett, M S et al (1988) '''Proteins encoded by bovine viral diarrhoea virus: The genomic organisation of a pestivirus.''' ''Virology'', 165(1), 200-208.