Neurological diseases and viral dynamics in the brains of neonatally borna disease virus-infected gerbils

Abstract

Borna disease virus (BDV) is a noncytolytic, neurotropic RNA virus that causes a chronic neurological disease in a wide variety of animal species. To develop a better understanding of the correlation between neurological disorders caused by BDV infection and virus distribution in the brain, we investigated viral dynamics in the central nervous system (CNS) of neonatally BDV-infected gerbils during the late stage of infection. Despite the severe symptoms and aggressive proliferation of BDV in the infected gerbils, no apparent neuroanatomical abnormalities or neuronal cell loss was observed in the infected gerbil brain. Furthermore, no or only minimal infiltration was observed in the infected gerbil brain. By in situ hybridization and real-time PCR analyses, we demonstrated that the predominant area of expression of BDV mRNA, as well as the protein, was shifted in the brain in association with progression of disease. In nondiseased gerbils, the virus replication was predominantly detected in the cerebral cortex and hippocampus of the CNS. On the other hand, diseased animals showed a high level of expression in the lower brain stem and cerebellum, especially in Purkinje cell neurons. These observations suggested that significant replication of the virus in specific areas of the CNS is critical for development of the neurological disorders in BDV-infected neonatal gerbils.