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Bovine Viral Diarrhoea Virus (view source)
Revision as of 18:31, 23 August 2010
, 18:31, 23 August 2010→Classification
Border disease, caused by Border disease virus (BDV) is the ovine pestivirus and was described by Hughes et al. in 1959. Congenital infection results in the birth of “hairy shaker” lambs, which suffer tonic-clonic tremors and have hairy rather than woolly coats (Sawyer, 1992). Severity of clinical signs can vary within a flock and among litter-mates.
Border disease, caused by Border disease virus (BDV) is the ovine pestivirus and was described by Hughes et al. in 1959. Congenital infection results in the birth of “hairy shaker” lambs, which suffer tonic-clonic tremors and have hairy rather than woolly coats (Sawyer, 1992). Severity of clinical signs can vary within a flock and among litter-mates.
===Virus Structure===
The BVDV genome comprises a single strand of positive sense RNA. By analysing the sequence of BVDV cDNA cloned into plasmid vectors, the genome has been found to be around 12.3Kb long (Donis, 1995). In infected cells, this is the only viral RNA present- no molecules of a subgenomic size are found. Figure 1.1 shows a diagrammatic interpretation of the BVDV genome.
Genomic information is read in a single, large open reading frame (ORF) that commences at nucleotide 386 of the RNA. The ORF is 3898 codons long, and contains no non-coding sequences. BVDV polyprotein is translated directly from the ORF, and mature viral proteins arise from this following endoproteinase cleavages by both viral and cellular mechanisms (Dubovi, 1990; Donis, 1995).
The 5’ and 3’ untranslated regions (UTRs) are located at either end of the ORF. Unlike eukaryotic mRNA, BVDV genomic RNA has neither the 5’ methylated cap nor the 3’ poly-A tail at these positions. Instead, the UTRs are significantly long, at approximately 385 and 226 nucleotides for the 5’ and 3’ UTRs respectively (Donis, 1995). This allows them to accommodate a variety of functions normally conferred by the 5’ cap and the poly-A region, including the control of translation initiation and RNA stability. Entry of replicases required to produce viral progeny from the RNA template is also guided by the UTRs.
Figure 1.1 also shows the proteins encoded by the BVDV genome. The polyprotein produced is 3898 amino acids long, and has a molecular weight of 438kD (Donis, 1995). The genomic RNA codes both structural and non-structural proteins.
The first structural protein coded is Npro, which has a protease action that generates the N-terminus of the next protein, C. C packages genomic RNA and provides interactions necessary for formation of the enveloped virion. Erns, E1 and E2 are all glycoproteins. Erns has an RNase activity that is probably involved in viral replication and pathogenesis (van Gennip, 2005). E1 is membrane-anchored and initiates the translocation of E2 to the virion envelope where it is highly antigenic, causing the production of neutralising antibodies following infection or vaccination (Donis, 1995).
The next protein is P7. Although P7 function is uncertain, studies have suggested that the C-terminal part acts as a signal sequence required for correct processing and membrane translocation of NS2 (Tautz et. al, 1999).
NS2-3 is the first non-structural protein translated. Sequence similarities are shown by NS2-3 to a region that in other flaviviruses is split into two distinct polypeptides, NS2 and NS3 (Donis, 1995). NS2-3’s N-terminus is homologous to NS2, and its C-terminus to NS3. After the first 6 hours of infection, NS3 is found exclusively in cytopathic biotypes expressed as a separate polypeptide, making it a marker of cytopathic BVDV (Donis, 1995). 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.
===Virus Genotypes===
==Transmission and Epidemiology==
==Transmission and Epidemiology==