Bovine viral diarrhoea and mucosal disease

Bovine viral diarrhoea and mucosal disease

L N D POTGIETER

Introduction

Bovine viral diarrhoea (BVD) and mucosal disease (MD) are two of several disease syndromes in cattle caused by bovine viral diarrhoea virus (BVDV). The primary target of BVDV appears to be the bovine embryo or foetus, resulting in embryonal/ foetal death, teratogenesis, persistent infection or inapparent infection with an immune response. A late consequence of some foetal infections is the birth of calves with persistent infections that subsequently result in the development of MD which is precipitated by the genesis of BVDV mutants in persistently infected animals or by superinfection by such mutants. Primary postnatal infections in cattle usually result in trivial BVD which is associated only with inappetance, fever and leukopenia. However, in recent years, instances of severe and sometimes fatal BVDV-induced disease of cattle characterized by fever, diarrhoea, respiratory disease and/or a generalized haemorrhagic syndrome have been reported.

Several detailed reviews on various facets of the disease have been published.5, 13, 17, 18, 19, 37, 54, 73, 105, 135, 164, 165

Bovine viral diarrhoea was first described in cattle in New York State, USA, in 1946 by Olafson and co-workers.243 The disease was characterized by abortions, fever, inappetance, diarrhoea, and ulceration of the gastrointestinal tract. The morbidity was high and the mortality in outbreaks was 4 to 8 per cent. Mucosal disease was initially known as ‘X disease’ and was first recorded in Canada, also in 1946, by Childs.244 Ramsey et al. coined the term ‘mucosal disease’ in 1953 based on their observations of the nature of the disease and lesions in Iowa cattle.245

Aetiology

Bovine viral diarrhoea virus is a member of the Pestivirus genus of the family Flaviviridae.54, 73 Currently, three species of pestiviruses are recognized; BVDV, Border disease virus and classical swine fever/hog cholera virus. For more information on these viruses, consult Border disease and : Hog cholera.

Bovine viral diarrhoea virions are spherical particles approximately 50 nm in diameter, with a tightly adherent envelope containing glycolipids (reviewed by Murphy et al.240). The virions are difficult to detect by negative-stain electron microscopy, but roughly spherical particles with a 20 to 25 nm core are readily detectable in infected cells where the virus replicates entirely within the cytoplasm.241 Because the virus has a lipid-rich envelope, it is susceptible to most common disinfectants.240

The BVDV genome consists of a single strand of RNA with positive polarity and contains one large open reading frame (gene) that encodes a polyprotein of approximately 4 000 amino acids (Figure 86.1). This open reading frame is preceded by a short untranslated region (UTR) that functions to initiate protein synthesis.163 Protein maturation is the consequence of co-translational and post-translational cleavage of the polyprotein by viral and host cell proteases. Except for the first protein encoded by the BVDV genome (Npro — a viral protease), the structural proteins are encoded by the first third of the genome (5’ end), whereas the non-structural proteins are encoded by the last two-thirds of the genome. Our knowledge of the exact functions of these proteins is still rudimentary.73, 199

The structural proteins include the internal capsid protein (C) and the virion surface envelope proteins. Erns (or E0) is only loosely associated with the virion and has intrinsic RNase activity. E1 is a transmembrane glycoprotein and forms a dimer on the virion surface with glycoprotein E2. The latter is the major viral glycoprotein and the principal target of virus-neutralizing antibodies.

The non-structural (NS) proteins are not incorporated into virions but probably function in viral replication. The NS5A and NS5B proteins appear collectively to constitute the polymerase responsible for viral RNA replication. Most virus isolates encode the NS2-3 protein that contains a serine protease motif. Some cytopathic strains also produce the NS2 and NS3 cleavage products of the NS2-3 protein. The NS3 protein has at least three enzymatic activities including the serine proteinase activity of the parent NS2-3 protein.

Two biotypes of BVDV are identifiable in the laboratory: non-cytopathic isolates that do not obviously affect the integrity of cultured cells and cytopathic isolates that induce cytopathic effects and the death of infected cells. At least two BVDV genotypes (types 1 and 2), unrelated to the biotype, exist75, 179, 181 and non-cytopathic and cytopathic isolates exist within each genotype. Genotypes are distinguished by the base sequence of the relatively conserved, 5’ untranslated region of their genomes.181 Therefore genotypes are differentiated by nucleic acid sequences that do not encode viral proteins. Most of the genotype 2 isolates were recovered from animals with acute haemorrhagic disease, from foetal bovine sera, and from persistently infected calves born to dams vaccinated against BVD.30, 75 Severe primary postnatal infections have been recognized only in recent years and this has led to speculation, which is supported by some experimental data, that the recently identified genotype 2 isolates are more virulent than the genotype 1 isolates.28, 81, 153 Although genotype 2 virus prevalence in the USA may appear to be...

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