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 protei ns. Bovine herpesvirus type 1 (BHV-1) causes respiratory and genital diseas es in cattle, whereas BHV-5 causes acute meningoencephalitis in calves, The gC gene sequence of these two viruses are substantially different. To dete rmine the contribution of the BHV-5 glycoprotein gC (gC5) to the neuropatho genesis of BHV-5, we have constructed two BHV-5 recombinants: gC-deleted BH V-5 (BHV-5gC Delta) and BHV-5 expressing BHV1 gC (BHV-5gC1). Neurovirulence properties of these viruses were analyzed using a rabbit seizure model tha t distinguishes BHV-1 and -5 based on their differential neuropathogeneses. Intranasal inoculations of BHV-5gC Delta and BHV-5gC1 viruses produced neu rological signs in 30% and 40% of the infected rabbits, respectively, Immun o-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 g C-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 in vade the hippocampus, but it did not invade the additional sites. Virus iso lation results suggest that these recombinants replicate less efficiently i n 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 so me areas of the olfactory pathway, Additionally, gC is important for BHV-5 neurovirulence in the olfactory pathway but it is not essential.