Bovine herpesvirus 5 glycoprotein E is important for neuroinvasiveness andneurovirulence in the olfactory pathway of the rabbit

Glycoprotein E (gE) is important for full virulence potential of the alphah erpesviruses in both natural and laboratory hosts. The gE sequence of the n eurovirulent bovine herpesvirus 5 (BHV-5) was determined and compared with that of the nonneurovirulent BHV-1. Alignment of the predicted amino acid s equences of BHV-1 and BHV-5 gE open reading frames showed that they had 72% identity and 77% similarity. To determine the role of gE in the differenti al neuropathogenesis of BHV-1 and BHV-5, we have constructed BHV-1 and BHV- 5 recombinants: gE-deleted BHV-5 (BHV-5gE Delta), BHV-5 expressing BHV-1 gE (BHV-5gE1), and BHV-1 expressing BHV-5 gE (BHV-1gE5). Neurovirulence prope rties of these recombinant viruses were analyzed using a rabbit seizure mod el (S. I. Chowdhury et al., J. Comp. Pathol. 117:295-310, 1997) that distin guished wild-type BHV-1 and -5 based on their differential neuropathogenesi s. Intranasal inoculation of BHV-5 gE Delta and BHV-5gE1 produced significa ntly reduced neurological signs that affected only 10% of the infected rabb its. The recombinant BHV-1gE5 did not invade the central nervous system (CN S). Virus isolation and immunohistochemistry data suggest that these recomb inants replicate and spread significantly less efficiently in the brain tha n BHV-5 gE revertant or wild-type BHV-5, which produced severe neurological signs in 70 to 80% rabbits. Taken together, the results of neurological si gns, brain lesions, virus isolation, and immunohistochemistry indicate that BHV-5 gE is important for efficient neural spread and neurovirulence withi n the CNS and could not be replaced by BHV-1 gE. However, BHV-5 gE is not r equired for initial viral entry into olfactory pathway.