Developmental injury to the cerebellum following perinatal Borna disease virus infection

Abstract

In rats infected as neonates, Borna disease virus (BDV) infection causes neuroanatomical, behavioral and physiological abnormalities without encephalitis. Neonatal infection with BDV provides a powerful model for studying the effects of virus replication on brain development without inflammation-induced brain damage. Here we report that neonatal BDV infection interfered with cerebellar development in the Lewis rat. Based on cerebellar cross-sectional area measurements, abnormal cerebellar growth was first noted between 7 and 14 days after infection. Reactive astrocytosis was evident by three days after infection, even without encephalitis, and even before identification of viral proteins in the cerebellum. While neonatal BDV infection caused a significant loss in granule cells, infected granule cells were not identified. BDV proteins were readily detected in the Purkinje cells. Thus, persistent BDV infection of Purkinje cells, but not granule cells, was associated with loss of granule cells during cerebellar development, in the absence of encephalitis.