Neuropathologic Study of Border Disease Virus in Naturally Infected Fetal and Neonatal Small Ruminants and Its Association With Apoptosis

Abstract

The present study describes the pathologic changes and cellular apoptosis in the central nervous system (CNS) of fetal and neonatal small ruminants infected with border disease virus (BDV), as demonstrated by immunohistochemistry and in situ hybridization. Abortions of ewes and goats were observed, as were births of lambs and kids with poor survival rates and nervous signs. Lesions included cerebellar hypoplasia, porencephaly, hydranencephaly, and nonsuppurative meningoencephalomyelitis with hypomyelinogenesis. Viral antigens and RNA were present in neuropil, glial, and neuronal cells, especially in periventricular areas, cerebellum, and brainstem. TUNEL positivity and labeling of anti-bax and anti-caspases 3, 8, and 9 were detected in BDV-infected CNSs, especially in glial and neuronal cells. The double immunostaining and TUNEL assay revealed that in BDV-infected animals, not only were BDV-infected glial and neuronal cells undergoing apoptosis, but so were uninfected cells in close vicinity of BDV-infected cells. The expression of activated caspases 3, 8, 9; bax; and TUNEL in glial and neuronal cells of the infected fetal and neonatal kids were significantly (P < .05) higher than those of the infected fetal and neonatal lambs. Yet, the expression of bcl-2 in the CNSs of the infected fetal and neonatal lambs was higher (P < .05) in neuronal and glial cells than in those of the infected fetal and neonatal kids. The results suggest that cell death in the BDV-infected CNS is induced by intrinsic and extrinsic cascades of apoptotic pathways.

Diagnostic pathology in microbial diseases of sheep or goats

“…They include cerebellar dysgenesis/hypoplasia (Supplementary material 21), particularly prominent in Border disease and Schmallenberg disease, internal hydrocephalus and/or hydranencephaly, which are less frequent in Border disease, and leucomalacia/porencephaly Infrequent occurrence of micrencephaly and lissencephaly has been described in experimental Border disease. Microscopic changes include lymphohistiocytic or necrotising meningoencephalitis and/or myelitis, with perivascular cuffing and multifocal glial-histiocytic inflammation, neuroparenchymal necrosis with gitter cells and mineralisation and neuronal chromatolysis and necrosis (Sawyer, 1992;MacLachlan et al, 2009;Toplu et al, 2011;van der Sluijs et al, 2011;Herder et al, 2012). Particularly prominent in Border disease are lesions of hypomyelination, cerebellar cortex dysplasia and necrosis/loss of Purkinje cells (Løken and Bjerkås, 1991;Sawyer, 1992;Toplu et al, 2011).…”

“…Microscopic changes include lymphohistiocytic or necrotising meningoencephalitis and/or myelitis, with perivascular cuffing and multifocal glial-histiocytic inflammation, neuroparenchymal necrosis with gitter cells and mineralisation and neuronal chromatolysis and necrosis (Sawyer, 1992;MacLachlan et al, 2009;Toplu et al, 2011;van der Sluijs et al, 2011;Herder et al, 2012). Particularly prominent in Border disease are lesions of hypomyelination, cerebellar cortex dysplasia and necrosis/loss of Purkinje cells (Løken and Bjerkås, 1991;Sawyer, 1992;Toplu et al, 2011). Viral proteins can be detected by immunohistochemistry in neurons of Schmallenberg virus infected foetuses (Herder et al, 2013) and in a variety of cell types in cases of Border disease (Thür et al, 1997).…”

First molecular detection and characterization of Akabane virus in small ruminants in Turkey

“…Congenital malformations in newborn lambs and kids, in addition to abortions in small ruminant flocks, have been reported previously in Turkey [20][21][22]. This study investigated the presence of teratogenic viruses in samples obtained from two geographically separate areas, from two different species, based on anamnestic information provided by farmers during the lambing seasons of 2013 and 2014, and using PCR, AKAV was found in these two small-ruminant flocks for the first time.…”

Intracerebral Inoculation of Mouse-Passaged Saffold Virus Type 3 Affects Cerebellar Development in Neonatal Mice

“…We speculated that a large number of Bergmann glial cells were infected with the AM-5Cb strain and died because of disruption of the balance in the interactions between Bergmann glial cells and Purkinje cells. Although there are no reports of hypoplasia after picornavirus infection, parvovirus, lymphocytic choriomeningitis virus, and border disease virus infections induce hypoplasia of the cerebellar cortex (70)(71)(72)(73). Borna disease virus also induces cerebellar disorders in neonatal rats (74,75).…”