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Timestamp: 2019-04-18 20:29:49+00:00

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Even though findings obtained from experimental Borna disease virus (BDV) infection of other species gave many insights into species-specific pathogenic processes, BDV infection of the rat is the most common model for studying the pathogenesis of Borna disease (BD). In infections in which MHC class II-restricted cytotoxic T-cell activity was elicited in vitro, there has been no direct evidence for in vivo antiviral effector cell lysis. Thus, it was interesting that initial reports suggested that CD4+ cells played the major role in the immunopathogenesis of BDV. Investigations of experimental adult BDV infection in other species replicated findings from the rat model and extended one&apos;s understanding of the pathogenesis of BD. Viral infections of the central nervous system (CNS) are a significant cause of congenital disease in newborns. Moreover, many neuropsychiatric disorders of children, such as autism, may result from early brain injury during critical periods of pre- or postnatal brain development. The hippocampal formation, especially neurons of the CA3 and CA4 areas, is one of the first targets of neonatal BDV infection. Damage to the cerebellum has also been observed in other perinatal virus infections, including lymphocytic choriomeningitis virus, rubella, mumps, rat parvovirus, or reovirus type III. The study of the pathogenesis of neurological diseases caused by BDV infection is a formidable challenge. Importantly, during the asymptomatic phase of the disease, the virus replication was predominantly detected in the cerebral cortex and hippocampus.
Cortical brain atrophy as a consequence of BDV infection in rats. Note the profound atrophy of the brain parenchyma and hydrocephalus ex vacuo (*) in the BDV-infected rat (A) compared to the intact brain parenchyma in the sham-inoculated rat (B). Original magnification, ×30 (present magnification, ×20). Hematoxylin-and-eosin staining was used. Courtesy of Thomas Bilzer.
Obese (left) and nonobese (right) rats infected with BDV as adults.
BDV antigen expression in PCs of the cerebellum at day 10 p.i. immunostaining of BDV nucleoprotein in sham-inoculated (A) and neonatally BDV-infected (B) Lewis rats. Note the expression of BDV antigen in many PCs in a BDV-infected rat (arrow). Original magnification, ×100 (present magnification, ×70). Courtesy of Aymeric Hans, Unité des virus lents, Institut Pasteur, Paris, France.
Degeneration of the DG of the hippocampus in neonatally BDV-infected rats at day 30 p.i. (A) Sham-inoculated rat; (B) BDV-infected rat. Note the disappearance of DG in the BDV-infected rat (arrowhead) compared to control DG. Hematoxylin and eosin staining was used. Original magnification, ×100 (present magnification, ×80).
Hypoplasia of the cerebellum following neonatal BDV infection at day 30 p.i. Shown are representative sagittal sections of the cerebellum of a sham-inoculated rat (A) and a BDV-infected rat (B). Hematoxylin and eosin staining was used. Original magnification, ×12.5 (present magnification, ×8).
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