Pathogenesis of Borna Disease in Rats: Immune-Mediated Viral Ophthalmoencephalopathy Causing Blindness and Behavioral Abnormalities

Abstract

Borna disease virus is an unclassified agent that causes a rare but fatal encephalitis in horses in Germany. In experimental animals the virus causes acute fatal encephalitis in some instances and chronic encephalitis with abnormal behavior in others. In initial studies of the pathogenesis of the latter disease in rats, the virus was shown to replicate only in the nervous system, with the greatest concentration of infectivity in the cerebrum and eyes. Viral replication continued indefinitely in both newborn and adult rats. The adult animals developed self-limiting, necrotizing encephalitis in the cerebrum, with inflammation spreading to the retina. Inflammation receded after two months, however, with concomitant cessation of necrosis; static hydrocephalus was observed at this point. Levels of viral replication were unaffected by these changes. Rats became frenzied and aggressive during the encephalitic period but became permanently passive and inactive after inflammation receded. Infected neonates and immunosuppressed adults did not become ill. The frenzied behavior and subsequent blindness in immunocompetent adults were therefore attributed to a uniquely transient immunopathologic reaction targeted to centers in the limbic system and retinal neurons.