Bovine viral diarrhea (BVD), bovine viral diarrhoea (UK English) or mucosal disease, previously referred to as bovine virus diarrhea (BVD), is an economically significant disease of cattle that is found in the majority of countries throughout the world. Worldwide reviews of the economically assessed production losses and intervention programs (e.g. eradication programs, vaccination strategies and biosecurity measures) incurred by BVD infection have been published. The causative agent, bovine viral diarrhea virus (BVDV), is a member of the genus Pestivirus of the family Flaviviridae.
BVD infection results in a wide variety of clinical signs, due to its immunosuppressive effects, as well as having a direct effect on respiratory disease and fertility. In addition, BVD infection of a susceptible dam during a certain period of gestation can result in the production of a persistently infected (PI) fetus.
PI animals recognise intra-cellular BVD viral particles as ‘self’ and shed virus in large quantities throughout life; they represent the cornerstone of the success of BVD as a disease.
Currently, it was shown in a worldwide review study that the PI prevalence at animal level ranged from low (≤0.8% Europe, North America, Australia), medium (>0.8% to 1.6% East Asia) to high (>1.6% West Asia). Countries that had failed to implement any BVDV control and/or eradication programmes (including vaccination) had the highest PI prevalence.
Virus classification and structure
BVDVs are members of the genus Pestivirus, belonging to the family Flaviviridae. Other members of this genus cause Border disease (sheep) and classical swine fever (pigs) which cause significant financial loss to the livestock industry.
Pestiviruses are small, spherical, single-stranded, enveloped RNA viruses of 40 to 60 nm in diameter.
The genome consists of a single, linear, positive-sense, single-stranded RNA molecule of approximately 12.3 kb. RNA synthesis is catalyzed by the BVDV RNA-dependent RNA polymerase (RdRp). This RdRp can undergo template strand switching allowing RNA-RNA copy choice recombination during elongative RNA synthesis.
Two BVDV genotypes are recognised, based on the nucleotide sequence of the 5’untranslated (UTR) region; BVDV-1 and BVDV-2. BVDV-1 isolates have been grouped into 16 subtypes (a –p) and BVDV-2 has currently been grouped into 3 subtypes (a – c).
BVDV strains can be further divided into distinct biotypes (cytopathic or non-cytopathic) according to their effects on tissue cell culture; cytopathic (cp) biotypes, formed via mutation of non-cytopathic (ncp) biotypes, induce apoptosis in cultured cells. Ncp viruses can induce persistent infection in cells and have an intact NS2/3 protein. In cp viruses the NS2/3 protein is either cleaved to NS2 and NS3 or there is a duplication of viral RNA containing an additional NS3 region. The majority of BVDV infections in the field are caused by the ncp biotype.
Epidemiology
BVD is considered one of the most significant infectious diseases in the livestock industry worldwide due to its high prevalence, persistence and clinical consequences.
In Europe the prevalence of antibody positive animals in countries without systematic BVD control is between 60 and 80%. Prevalence has been determined in individual countries and tends to be positively associated with stocking density of cattle.
BVDV-1 strains are predominant in most parts of the world, whereas BVDV-2 represents 50% of cases in North America. In Europe, BVDV-2 was first isolated in the UK in 2000 and currently represents up to 11% of BVD cases in Europe.
Transmission of BVDV occurs both horizontally and vertically with both persistently and transiently infected animals excreting infectious virus. Virus is transmitted via direct contact, bodily secretions and contaminated fomites, with the virus being able to persist in the environment for more than two weeks. Persistently infected animals are the most important source of the virus, continuously excreting a viral load one thousand times that shed by acutely infected animals.
Pathogenesis
Acute, transient infection
Following viral entry and contact with the mucosal lining of the mouth or nose, replication occurs in epithelial cells. BVDV replication has a predilection for the palatine tonsils, lymphoid tissues and epithelium of the oropharynx.
Phagocytes take up BVDV or virus-infected cells and transport them to peripheral lymphoid tissues; the virus can also spread systemically through the bloodstream. Viraemia occurs 2–4 days after exposure and virus isolation from serum or leukocytes is generally possible between 3–10 days post infection.