title: Bovine herpesvirus 5 glycoprotein E is important for neuroinvasiveness and neurovirulence in the olfactory pathway of the rabbit.
abstract: Glycoprotein E (gE) is important for full virulence potential of the alphaherpesviruses in both natural and laboratory hosts. The gE sequence of the neurovirulent bovine herpesvirus 5 (BHV-5) was determined and compared with that of the nonneurovirulent BHV-1. Alignment of the predicted amino acid sequences 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 differential neuropathogenesis of BHV-1 and BHV-5, we have constructed BHV-1 and BHV-5 recombinants: gE-deleted BHV-5 (BHV-5gEDelta), BHV-5 expressing BHV-1 gE (BHV-5gE1), and BHV-1 expressing BHV-5 gE (BHV-1gE5). Neurovirulence properties of these recombinant viruses were analyzed using a rabbit seizure model (S. I. Chowdhury et al., J. Comp. Pathol. 117:295-310, 1997) that distinguished wild-type BHV-1 and -5 based on their differential neuropathogenesis. Intranasal inoculation of BHV-5 gEDelta and BHV-5gE1 produced significantly reduced neurological signs that affected only 10% of the infected rabbits. The recombinant BHV-1gE5 did not invade the central nervous system (CNS). Virus isolation and immunohistochemistry data suggest that these recombinants replicate and spread significantly less efficiently in the brain than 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 signs, brain lesions, virus isolation, and immunohistochemistry indicate that BHV-5 gE is important for efficient neural spread and neurovirulence within the CNS and could not be replaced by BHV-1 gE. However, BHV-5 gE is not required for initial viral entry into olfactory pathway.
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas 66506, USA. Chowdh@vet.ksu.edu
authors.forename: S I
authors.initials: SI
authors.lastname: Chowdhury
authors.forename: B J
authors.initials: BJ
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Ozkul
authors.forename: M L
authors.initials: ML
authors.lastname: Weiss
mesh_terms: D018138:Alphaherpesvirinae / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000032:analysis* / Q000235:genetics; D002417:Cattle; D002460:Cell Line; D002494:Central Nervous System Infections / Q000662:veterinary*; D002540:Cerebral Cortex / Q000276:immunology / Q000821:virology; D003937:Diagnosis, Differential; D004195:Disease Models, Animal; D017353:Gene Deletion; D015321:Gene Rearrangement; D006566:Herpesviridae Infections / Q000662:veterinary*; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009154:Mutation; D009833:Olfactory Pathways / Q000276:immunology / Q000821:virology*; D016366:Open Reading Frames; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology; D011995:Recombination, Genetic; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D014774:Virulence
chemical_list: D000956:Antigens, Viral; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C414993:glycoprotein E, bovine herpesvirus type 5