Epizootic haemorrhagic disease

Previous authors: N J MACLACHLAN AND B I OSBURN

Current authors:
N J MACLACHLAN - Distinguished Professor Emeritus, BVSc, PhD, Dip ACVP, Department of Pathology, Microbiology and Immunology, VetMed 3A, School of Veterinary Medicine / Veterinary Tropical Diseases, Faculty of Veterinary Science, University of California / University of Pretoria, One Shields Ave, Davis, California, 95616, United States
G SAVINI - Head of the Animal Health Department and of the National and OIE Reference Laboratory for BT, DVM, PhD, Istituto Zooprofilatico Sperimentale dell'Abruzzo e Molise "G. Caporale" Via Campo Boario, Teramo, 64101, Italy
B I OSBURN - Emmeritus Proffessor, Faculty of Veterinary Science, University of California / University of Pretoria, One Shields Ave, Davis, California, 95616, United States

GENERAL INTRODUCTION: REOVIRIDAE

Introduction

Epizootic haemorrhagic disease (EHD) is a Culicoides-transmitted haemorrhagic viral disease of wild and domestic ruminants, particularly white-tailed deer (Odocoileus virginianus).^{38, 58, 63, 73} The causative agent, EHD virus (EHDV), is an orbivirus that is very closely related to bluetongue virus (BTV) and both EHDV and BTV cause a similar disease in susceptible ruminants.^{24, 30, 38, 41, 57, 58, 62, 68, 73}

Epizootic haemorrhagic disease was first described in white-tailed deer in North America in 1955 and substantial epidemics have since been described among populations of white-tailed deer and, to a lesser extent, other wild ruminant species including pronghorn antelope (Antilocapra americana), and bighorn sheep (Ovis canadensis).^{16, 19, 24, 38, 52} Infection with EHDV has also been documented in many other regions of the world.^{9, 20, 21, 29, 33, 35, 46-48, 54, 55, 59, 71, 73} Epizootic haemorrhagic disease virus is generally not regarded as a pathogen of domestic ruminants,^{1, 10, 17, 32, 33, 70} a notable exception is Ibaraki virus, a specific  EHDV that caused an extensive outbreak of disease in cattle in Japan in the late summer and autumn of 1959 and 1960, and continues to cause disease amongst cattle in the Far East and perhaps elsewhere (see Ibaraki disease in cattle). Similarly, in recent years, EHDV has increasingly been identified as the cause of a disease syndrome of oral ulceration and coronitis in cattle in the Mediterranean Basin, Reunion Island, South Africa, South America and the USA.^{7, 13, 15, 18, 21, 28, 34-36, 39, 52, 63, 67, 72, 81} The increasing number of clinical cases reported in cattle has raised concerns amongst international authorities and in 2008, the disease was included in the OIE list of multispecies/ transboundary diseases.⁴

Aetiology

Epizootic haemorrhagic disease virus is a member of the family Reoviridae, subfamily Sedoreovirinae, genus Orbivirus.⁶²  It is closely related to BTV, the prototype virus of the genus Orbivirus, and to African horse sickness virus.⁴⁴ Viruses within the EHDV serogroup all share group-specific serologic cross-reactivity, and at least seven distinct serotypes are distinguished on the basis of neutralization tests with type-specific antisera and genetic and phylogenetic analyses.⁶² A novel additional serotype detected in an alpaca in South Africa has been proposed.⁸⁰ The particles of EHDV are non-enveloped and include a genome of ten double-stranded RNA segments. The virion consists of two protein shells, with an inner ‘core’ that consists of viral proteins (VP) VP1, VP3, VP4, VP6 and VP7 and an outer shell of VP2 and VP5. Five nonstructural (NS) proteins (NS1, NS2, NS3/3A, NS4)¹⁴ also are produced in EHDV-infected cells. The coding assignments and functions of each protein are identical to those of BTV (see Bluetongue).

As for BTV, there is a strong correlation between EHDV genome-sequences and the geographic origin of the strains (topotypes)^5-7 but no relationship exists between serotype and virulence. Like other orbiviruses, EHDV has a segmented genome and can undergo genetic reassortment. Individual genes also undergo genetic drift thus there is considerable genetic variation amongst the strains of EHDV that circulate within endemic regions. As an example, at least 3 different serotypes of EHDV currently circulate in North America, one of which (EHDV serotype 6) is a relatively recently introduced serotype that spread into the southeastern United States from the adjacent Caribbean ecosystem. Interestingly, however, only strains of EHDV serotype 6 that include reassorted genes from the historically endemic EHDV serotypes 1 and 2 were apparently able to expand their range beyond the southeastern United States.^{3, 75, 78}

The original Ibaraki virus that was first described in Japan in 1959 is serologically related to the prototype strain of EHDV serotype 2 that was originally isolated in Alberta in 1964 (see Ibaraki disease in cattle). The serotype-specific L2 gene of this Ibaraki virus shares only partial homology (72 per cent) with isolates of EHDV serotype 2 from the USA,⁵⁶  whereas the sequence of genes encoding core proteins (VP3, VP7) of Ibaraki virus are more conserved and very similar to those of Australian strains of EHDV.⁴³ The similarity of the core protein genes of Australian strains of EHDV and Ibaraki virus suggests that they are included in an Asian ‘topotype’ of EHDV. Interestingly, recent outbreaks of Ibaraki-like disease among cattle in Japan were caused by EHDV serotypes 6 and 7, not EHDV 2.^{46, 64} These same EHDV...