title: A glycine-rich bovine herpesvirus 5 (BHV-5) gE-specific epitope within the ectodomain is important for BHV-5 neurovirulence.
abstract: The bovine herpesvirus 5 (BHV-5) gE ectodomain contains a glycine-rich epitope coding region (gE5 epitope), residues 204 to 218, that is significantly different from the corresponding gE region of BHV-1. Deletion of the gE epitope significantly reduced the neurovirulence of BHV-5 in rabbits. Pulse-chase analyses revealed that the epitope-deleted and wild-type gE were synthesized as N-glycosylated endoglycosidase H-sensitive precursors with approximate molecular masses of 85 kDa and 86 kDa, respectively. Like the wild-type gE, epitope-deleted gE complexed with gI and was readily transported from the endoplasmic reticulum. Concomitantly, the epitope-deleted and wild-type gE acquired posttranslational modifications in the Golgi leading to an increased apparent molecular mass of 93-kDa (epitope-deleted gE) and 94-kDa (wild-type gE). The kinetics of mutant and wild-type gE processing were similar, and both mature proteins were resistant to endoglycosidase H but sensitive to glycopeptidase F. The gE epitope-deleted BHV-5 formed wild-type-sized plaques in MDBK cells, and the epitope-deleted gE was expressed on the cell surface. However, rabbits infected intranasally with gE epitope-deleted BHV-5 did not develop seizures, and only 20% of the infected rabbits showed mild neurological signs. The epitope-deleted virus replicated efficiently in the olfactory epithelium. However, within the brains of these rabbits there was a 10- to 20-fold reduction in infected neurons compared with the number of infected neurons within the brains of rabbits infected with the gE5 epitope-reverted and wild-type BHV-5. In comparison, 70 to 80% of the rabbits exhibited severe neurological signs when infected with the gE5 epitope-reverted and wild-type BHV-5. These results indicated that anterograde transport of the gE epitope-deleted virus from the olfactory receptor neurons to the olfactory bulb is defective and that, within the central nervous system, the gE5 epitope-coding region was required for expression of the full virulence potential of BHV-5.
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas 66506, USA.
authors.forename: A
authors.initials: A
authors.lastname: Al-Mubarak
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: S I
authors.initials: SI
authors.lastname: Chowdhury
mesh_terms: D000818:Animals; D001921:Brain / Q000821:virology; D002417:Cattle; D002460:Cell Line; D018792:Encephalitis, Viral / Q000503:physiopathology* / Q000821:virology; D000939:Epitopes / Q000737:chemistry*; D017353:Gene Deletion; D005998:Glycine / Q000737:chemistry; D006566:Herpesviridae Infections / Q000503:physiopathology / Q000821:virology; D025881:Herpesvirus 5, Bovine / Q000235:genetics / Q000472:pathogenicity*; D008590:Meningoencephalitis / Q000503:physiopathology* / Q000821:virology; D011817:Rabbits; D011995:Recombination, Genetic; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000276:immunology
chemical_list: D000939:Epitopes; D014759:Viral Envelope Proteins; C414993:glycoprotein E, bovine herpesvirus type 5; D005998:Glycine