Pathogenesis of meningoencephalitis in rabbits by bovine herpesvirus type-5 (BHV-5)

This article describes the main aspects of bovine herpesvirus type-5 (BHV-5) neurologic infection and disease in rabbits, a candidate animal model for studying BHV-5 neuropathogenesis. Intranasal inoculation of weanling rabbits with a Brazilian BHV-5 isolate produced neurological disease and death in 78.8% (26/33) of the animals. Neurological signs started as early as 5 days post-inoculation and lasted from 10-12 hours up to several days. Most animals evolved to a moribund state or death within 24 (69.2%) to 48 hours (88.5%). Neurological disease was characterized by excitability or depression, tremors, bruxism, walking or running in circles, backward arching of the head and body, incoordination, backward and sideways falling, paddling, profound depression and death. Moderate levels of infectivity were detected in several areas of the brain, most consistently in the ventro-lateral hemisphere (in 16 out of 20 animals), anterior cerebrum (15/20), midbrain (11/20), dorso-lateral hemisphere (10/20) and pons (12/26). Infectious virus was also recovered from the olfactory bulb (9/20), medulla oblongata (10/26), cerebellum (7/20), posterior cerebrum (5/20) and trigeminal ganglia (4/20). No gross lesions were observed. Microscopic lesions were mild and consisted of non-suppurative meningitis, mononuclear perivascular cuffing and focal gliosis. These changes were observed most consistently in the ventro-lateral hemisphere and anterior cerebrum. Passive immunity partially protected rabbits from BHV-5-induced encephalitis. Rabbits born to immunized dams showed a significative delay in the onset of clinical disease and reduced morbidity and mortality rates compared to rabbits born to unvaccinated dams. These results demonstrate that BHV-5-induced neurological disease can consistently be reproduced in rabbits and point towards the use of this species as an animal model to study BHV-5 neuropathogenesis.