Border disease

P F NETTLETON

GENERAL INTRODUCTION: FLAVIVIRIDAE

Introduction

Border disease (BD) is a congenital virus disease of sheep and goats initially reported in 1959 from the border region of England and Wales and since recorded in other parts of Europe, North America, Australia, New Zealand, the Middle East and North Africa. The disease has also recently been confirmed by immunohistochemical demonstration of Border disease virus (BDV) in the brains of hairy-shaker lambs in South Africa.¹⁵ Some of these lambs also showed cerebellar hypoplasia. Border disease in sheep is characterized by barren ewes, abortion, stillbirths and the birth of small weak lambs, some of which show tremor, abnormal body conformation and hairy fleeces (’hairy-shaker’ or ‘fuzzy’-lambs) sometimes with excessive pigmentation. In some outbreaks no hairy-shaker lambs are born and the disease is difficult to distinguish from other causes of abortion. Occasionally the number of lambs born is apparently normal, and veterinary advice is sought only when a group of lambs fails to thrive and the number of scouring and dying lambs is abnormally high. Infection in goats is rare with abortion being the main presenting sign.

Aetiology

The cause of BD is a virus serologically related to bovine viral diarrhoea (BVD) virus and classical swine fever (CSF) virus, the three viruses being grouped in the genus Pestivirus within the family Flaviviridae. They are named after the diseases from which they were first isolated. Traditionally, pestiviruses isolated from pigs have been termed CSFV, those from cattle BVDV and those from sheep BDV. Cross-infection between these animal species occurs readily and the viruses are now grouped by their reactivity to monoclonal antibodies and their nucleotide sequences at selected genomic regions. Pestiviruses are enveloped, spherical particles approximately 50 nm in diameter in which the genome is a positive single-stranded RNA molecule. Virtually all pestivirus isolates from sheep and goats are noncytopathic in cell culture, but occasional cytopathic viruses have arisen following integration of cellular sequences into the viral genome.⁴

From studies with monoclonal antibodies and phylogenetic analysis of genomic sequences a consensus is emerging that there are four principal genotypes of pestiviruses: BVDV-1, BVDV-2, BDV and CSFV.^{7, 20, 24, 28} Other pestiviruses from wild ruminants do not fit into any of these groups and constitute separate virus types. A giraffe (Giraffa camelopardalis) isolate represents a single type, while pestiviruses isolated in 1996 from a reindeer (Rangifer tarandus) and a bison (Bison bonasus) kept in the same zoo form another separate type.⁵ While CSF viruses are predominantly restricted to pigs, examples of the other three principal genotypes have all been recovered from sheep. Examination of seven goat isolates has shown them to be BVDV-1 types.^{6, 23}

Comparison of the available complete genomic sequences pestiviruses has revealed that the BD viruses are closer to CSF viruses than they are to BVD viruses.^{7, 24}

There are relatively few reports of cross-neutralization experiments involving pestiviruses from sheep and goats. Nevertheless, four principal serological groups have been identified, which correlate with the monoclonal antibody and genotype groupings.²¹ A recent comparison of ten sheep pestiviruses from the UK showed two groups of serologically distinguishable BDV isolates, one group related to Moredun BDV and the other to the Weybridge and BVD viruses.¹⁹ These antigenic differences correlate well with genotyping results since all the Moredun BDV related isolates type as true BDVs whereas representatives of the other group all fit into the BVDV-1 genogroup. Genotyping studies on a total of 38 UK sheep isolates showed that 23 (60 per cent) were true BD viruses and ten (26 per cent) belonged to the BVDV-1 group. A further five isolates (13 per cent) belonged to the BVDV-2 group.²⁸

It is known that representatives of BD viruses and BVD-1 viruses are serologically distinct and do not cross-protect,which implies that any BD vaccine should contain at least one representative from each of the BDV and the BVDV-1 groups.²⁷ Cross-protection between BVDV-2 and BVDV-1 and BD viruses needs to be studied further. Recent foetal cross-protection studies in pregnant ewes have shown that foetuses of ewes experimentally infected with BVDV-1 were protected from challenge with BVDV-2, whereas foetuses of ewes experimentally infected with the BVDV-2 virus were infected after challenge with BVDV-1.²²

Epidemiology

Sheep-to-sheep contact is the principal way in which BDV is transmitted and the most potent source of virus is the persistent excretor. Flocks with no previous experience of the disease are particularly vulnerable. Purchased, persistently infected, young ewes have been shown to introduce BDV into such flocks.⁸

Persistently infected lambs that reach maturity often have reduced fertility. Ewes that conceive either abort or produce persistently infected lambs sometimes over a period of years. Persistently infected rams usually have small soft testicles but can transmit virus in their semen as well as nasal/ocular secretions and saliva. The speed of virus spread in a susceptible flock exposed to one or more persistent excretors will depend on the contact between sheep. Under field conditions, intimate contact at mating time or gathering...