PATHOGENESIS AND EPIDEMIOLOGY OF BORDER DISEASE Nettleton Pf To cite this version: Nettleton Pf. PATHOGENESIS AND EPIDEMIOLOGY OF BORDER DISEASE. Annales de Recherches Vétérinaires, INRA Editions, 1987, 18 (2), pp.147-155. hal-00901704 HAL Id: hal-00901704 https://hal.archives-ouvertes.fr/hal-00901704 Submitted on 1 Jan 1987 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. PATHOGENESIS AND EPIDEMIOLOGY OF BORDER DISEASE NETTLETON PF Moredun Research lnstitute, 408 Gilmerton Road, Edinburgh, EH 1 7JH, Scotland meeting on Pestivirus, 8th April 1986, Liege Résumé PATHOGÉNIE ET ÉPIDÉMIOLOGIE DE LA MALADIE DE BORDER. ― Il s’agit d’une brève synthèse des connaissances sur la pathogénie de l’infection par le virus de la maladie de Border chez le mouton. C’est lorsque ce virus infecte une femelle gestante sensible que les conséquences en sont les plus graves. Le virus traverse rapidement la barrière placentaire et peut provoquer éventuellement la mort du foetus suivie de résorption, de momification ou de mortinatalité. Certains agneaux survivent et naissent atteints à un degré variable de tremblements et/ou présentant une laine hirsute. La plupart de ces agneaux hirsutes et trembleurs meurent rapidement après la naissance, mais les survivants guérissent progressivement. Ces survivants, ainsi que certains individus apparemment normaux, demeurent infec- tés de manière persistante par le virus et l’excrètent continuellement, généralement leur vie durant. Ces animaux infectés persistants jouent un rôle-clé dans l’épidémiologie de l’infection et peuvent être responsables de son extension à un troupeau indemne. Les bovins pâturant avec des moutons consti- tuent également une importante source potentielle de pestivirus susceptibles de provoquer la maladie de Border, puisque dans certains troupeaux 1 à 3 % des bovins sont infectés de manière persistante par un pestivirus. Les résultats d’études des relations antigéniques entre des souches de pestivirus bovin (virus BVD) et ovin (virus de la maladie de Border) isolées en Écosse sont présentés: on peut en conclure que si une seule souche de virus BVD pourrait suffire pour la vaccination des bovins, ce serait insuffisant dans le cas de la maladie de Border, puisqu’on a identifié deux souches antigéniquement distinctes du virus ovin. Un vaccin contre la maladie de Border, pour être efficace, doit donc être à même de protéger les moutons contre ces deux souches et, idéalement, un vaccin à usage bovin devrait également contenir ces deux souches. Border disease (BD) is a congenital infection of The pathogenesis of diseases caused by or sheep and goats. Characteristic evidence of the associated with BD virus infection disease in sheep includes a history of barren ewes, abortions, stillbirths and the birth of weak lambs, a The most serious consequences occur when variable percentage of which show tremor, abnor- BDV infects susceptible ewes during pregnancy. mal body conformation and hairy fleeces. Experimental infections of pregnant ewes have shown while the maternal infection is The cause of BD is a virus serologically related that, usually to bovine virus diarrhoea virus (BVDV) and hog subclinical or mild, the virus can cause a wide cholera virus (HCV), the three viruses being grou- range of fetal disease varying from death and abortion ped in the genus Pestivirus in the family Togavi- to the birth of live apparently normal ridae (Plant et al 1973, Porterfield et al 19781. lambs some of which may be persistently infected with virus for the rest of their lives. Pestiviruses isolated from sheep are termed BDD Experimental virus IBDV) and those from cattle BVDV but sheep infections of pregnant goats have produced a high isolates will infect cattle and vice versa. incidence of fetal death and abortion (Barlow et al 1975). Recent comprehensive reviews by Barlow and Patterson (1982) and (1985) have cove- Terpstra Fetal infection red all aspects of BD while the biology of the pestiviruses has been compared with that of other The most important route of fetal infection is non-arthropod borne togaviruses particularly transplacental. Exposure of susceptible pregnant rubella virus of man (Horzinek 1981, Van Oirschot ewes results in viraemia with spread of virus to the 19831. The purposes of this paper are to review placenta (French et al 1974). Transmission to the briefly the pathogenesis of diseases caused by fetus has been achieved by infected semen but BDV, to summarise our present knowledge of the under natural conditions this is unlikely to be a epidemiology of BD, and finally to present new major route of infection (Gardiner and Barlow data on the antigenic relationships between 19811. The placentitis may be severe enough to isolates of BD and BVD viruses. contribute to the early fetal death and abortion which occur in some cases, but if the pregnancy is 150 days gestation period (Fahey and Morris sustained the placentitis heals in about 25 days 19781. (Barlow 1972). Knowledge of the fetal response to BDV infec- Once the placenta has been penetrated the tion has been derived predominantly from experi- virus is protected from the maternal immune ments in which the fetus has been infected via the response which has occurred following infection dam. The speed with which the virus crosses the (Gardiner 1982). The fetus and virus are on their placenta is not known accurately so that the own. The ultimate outcome of this relationship actual timing of fetal infections is only approxi- depends on several factors, the major one of mate. Nevertheless there is strong evidence that which is the stage of fetal development at which lambs born to ewes infected after 80 days gesta- infection occurs. The most serious consequences tion are clinically normal with neutralising anti- follow exposure during early pregnancy. Other body to BDV but no infectious virus in their blood. factors include the strain and dose of the virus, the Such lambs have a characteristic nodular periarte- breed of the fetus and its ability to repair damage. ritis, suggestive of a cell-mediated allergic reac- The age at which the fetus gains immunological tion, and BDV antigen has been shown to be asso- competence is critical in determining the distribu- ciated with these lesions (Zakarian et al 1976, tion and persistence of virus, which, in turn, Gardiner et al 1980). influences the extent of fetal damage. The ovine The outcome of fetal exposure to virus at other fetus can first respond to an antigenic stimulus stages of gestation is less predictable. The produc- between 64 and 82 days of its approximately tion of clinically affected &dquo;hairy-shaker&dquo; lambs has been achieved most consistently by infecting explain the inflammatory and necrotic lesions of ewes between 50 and 63 days gestation, that is, AP. before the onset of immune competence. In such The outcome of early fetal infection clearly lambs viral antigen is widespread (Terpstra 19781. depends on a very complex interaction between There are, however, few histopathological the infecting virus, the ewe and the fetus. Virus changes in the viscera, although reduced thymus strains vary in their antigenicity and pathogenic weight and poorly developed lymphatic nodules potential. Previous exposure of the ewe to pestivi- and a scarcity of lymphocytes in the spleen have ruses can prevent or modify the attack on the been noted (Richardson 1982). Typically there is fetus, while the fetus, depending on its stage of no evidence of any inflammatory reaction. The development, can react immunologically and rid principal pathological finding, myelin deficiency in itself of the virus, but sometimes at the cost of the central nervous system (CNS), is thought to causing severe malformations. Early fetal infection result from direct viral action on oligodendrocyte without an immune response frequently causes precursors, leaving a deficit of mature myelin- fetal death which may result in resorption, forming cells at critical stages of CNS develop- mummification, abortion or stillbirth. Other lambs ment (Barlow 1982). Precolostral blood samples survive to term, however, and many of these are from &dquo;hairy-shaker&dquo; lambs do not contain specific persistently infected with and apparently immuno- neutralising antibodies against BDV, but infectious tolerant to their infecting virus. Clinically affected virus is isolated easily. Such lambs are tolerant to lambs have a low chance of survival; many die the virus and have a persistent infection usually for early in life while survivors have a poor growth life (Plant et al 19771. rate and an increased susceptibility to intercurrent Following some experimental BDV infections at disease. Less severely affected and apparently 50-55 days gestation, inflammatory lesions normal lambs can survive for years in spite of heavily infiltrated with macrophages and mononu- persistent infection with BDV (Terpstra 1981). clear cells, and liquefactive necrosis have been Persistent infection in life seen in the granuloprival layers of the CNS. These post-natal lesions were seen within 21 days of infection in Persistent infections usually continue into post- sacrificed fetuses and were considered to be the natal life and are characterised by a generalised cause of severe brain malformations seen in lambs infection in the host, which constantly sheds infec- surviving to term. The malformations included tious virus into the environment. After levels of hydranencephaly, porencephaly and cerebellar BDV colostral antibody have waned persistently hypoplasia, and some lambs also had arthrogrypo- infected lambs are viraemic and have no, or low, sis. Affected lambs had none of the clinical or titres of BDV neutralising antibody.