Neurovirulence of Glycoprotein C(gC)-deleted Bovine Herpesvirus Type-5 (BHV-5) and BHV-5 Expressing BHV-1 GC in a Rabbit Seizure Model

Herpesvirus glycoprotein C (gC) is one of the major virus attachment proteins. Bovine herpesvirus type 1 (BHV-1) causes respiratory and genital diseases in cattle, whereas BHV-5 causes acute meningoencephalitis in calves. The gC gene sequence of these two viruses are substantially different. To determine the contribution of the BHV-5 glycoprotein gC (gC5) to the neuropathogenesis of BHV-5, we have constructed two BHV-5 recombinants: gC-deleted BHV-5 (BHV-5gCDelta) and BHV-5 expressing BHV1 gC (BHV-5gC1). Neurovirulence properties of these viruses were analyzed using a rabbit seizure model that distinguishes BHV-1 and -5 based on their differential neuropathogeneses. Intranasal inoculations of BHV-5gCDelta and BHV-5gC1 viruses produced neurological signs in 30% and 40% of the infected rabbits, respectively. Immuno-histochemistry results showed that the number of infected neurons was 2 - 4-fold less with the gC-deleted BHV-5 than with the wild-type BHV-5. The gC-deleted BHV-5 did not invade the hippocampus but invaded additional sites not invaded by wild-type BHV-5. Similarly, the BHV-5gC1 virus failed to invade the hippocampus, but it did not invade the additional sites. Virus isolation results suggest that these recombinants replicate less efficiently in the brain than the wild-type and gC-revertant viruses. However, compared to the gC-deleted BHV-5, the gC-exchanged BHV-5gC1 replicated better within the CNS. These results indicate that gC regulates BHV-5 neurotropism in some areas of the olfactory pathway. Additionally, gC is important for BHV-5 neurovirulence in the olfactory pathway but it is not essential.