Neurovirulence and neuroinvasiveness of bovine herpesvirus type 1 and 5 in rabbits

In order to determine the capacity of bovine herpesvirus type I and 5 (BHV-1 and BHV-5) to invade, multiply and spread along the central nervous system (CNS) (neuroinvasiveness), as well as their potential to induce neurological illness (neurovirulence), 30 to 35 days old rabbits were inoculated with the BHV-5 strain EVI 88 / 95 and Los Angeles and Cooper BHV-1 strains, by the intrathecal (IT) and intranasal (IN) routes. The BHV-5 strain induced severe neurological clinical signs in 100% (12/12) of the rabbits inoculated by both routes. Histopathological examination revealed multifocal non-suppurative meningoencephalitis, characterized by multifocal gliosis and perivascular cuffing. Virus was recovered from many parts of the brain. Both BHV-1 strains, when inoculated via IT route, were not neurovirulent. The strain Los Angeles, after IN inoculation, induced signs of severe respiratory disease (7/7), as well as signs of neurological impairment, indistinguishable from those induced by BHV-5, in 57% (4/7) of the infected rabbits. However, the rabbits with nervous signs revealed at histopathology vasculitis and thrombosis in lungs and brain, the latter with foci of neuronal necrosis, but no lesions indicative of encephalitis, suggesting that neural damage was probably consequent to tissue anoxia. The BHV-1 strain Cooper, after IN inoculation, induced only mild signs of respiratory disease. These findings indicate that the BHV-5 strain was both neuroinvasive and neurovirulent, since it was capable of invading, spreading and multiplying in the rabbits' brains by both routes of inoculation, yet causing neurological disease, apparently consequent to virus induced neural damage. The BHV-1 Los Angeles strain was not neuroinvasive, whereas its neurovirulence was probably consequent to tissue anoxia, which histologically seemed not to be related to direct viral pathogenic effect. The BHV-1 strain Cooper was neither neurovirulent nor neuroinvasive for rabbits. It is possible that these observations bear relationship with the frequent association of BHV-5 with encephalitis in cattle, as opposed to BHV-1 encephalitis, which is a rare event in nature.