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

Abstract

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 ( No gross lesions were observed. Microscopic lesions were mild and consisted of nonsuppurative 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.

Experimental infection of rabbits with a recombinant bovine herpesvirus type 5 (BoHV-5) gI, gE and US9-negative

“…We believe that differences in age and breed of the infected rabbits could not justify such discrepancies, since these were comparable in both experiments. On the other hand, differences between virus strains might be a relevant source of variation, since it has been shown that different BoHV-5 isolates may significantly differ in their neurovirulence (Silva et al 1999, Beltrão et al 2001. When inoculated in older animals, the recombinant virus was apathogenic, contrasting with the effect of the wild type virus infection (which caused death in 55.5 % of infected animals).…”

“…Before infection rabbits were anesthesized with 2 mg of tiletamine/zolazepam (Zoletil, Virbac) and inoculated into each paranasal sinuses with a total volume of 0.5mL as described previously (Brown & Field. 1990, Silva et al 1999). …”

O Herpesvírus bovino tipo 5 (BoHV-5) pode utilizar as rotas olfatória ou trigeminal para invadir o sistema nervoso central de coelhos, dependendo da via de inoculação

“…Os animais dos Grupos 1 e 2 foram inoculados pela via intranasal (IN), através de aberturas dorso-laterais dos seios paranasais (protocolo adaptado por Silva et al 1999). Para tal, os animais foram previamente anestesiados com 2mg de Tiletamina/Zolazepam (Zoletil, Virbac).…”

Neuropatogênese experimental da infecção pelo herpesvírus bovino tipo 5 em coelhos

“…Em particular, os coelhos têm sido amplamente utilizados para estudar vários aspectos da neuropatogenia da infecção pelo BoHV-5, pois desenvolvem infecção e doença neurológica com certas similaridades àquela observada em bovinos (Meyer et al 1996, Chowdhury et al 1997, Silva et al 1999b.…”

“…Os primeiros estudos nesta espécie foram realizados para caracterizar os aspectos virológicos, clíni-cos e patológicos da infecção neurológica aguda, e avaliar a adequação desta espécie como modelo experimental para esse vírus (Silva et al 1999b). A partir desses estudos, vários aspectos relacionados com a patogenia, imunidade e terapia antiviral foram abordados (Beltrão et al 2000, Spilki et al 2000, Diel et al 2005, Dezengrini et al 2008a.…”