title: Glycoprotein E (gE) specified by bovine herpesvirus type 5 (BHV-5) enables trans-neuronal virus spread and neurovirulence without being a structural component of enveloped virions.
abstract: Bovine herpesvirus 5 (BHV-5) is a neurovirulent alpha-herpesvirus that causes fatal encephalitis in calves. We previously demonstrated that deletion of a glycine-rich epitope in the gE ectodomain dramatically reduced BHV-5 neurovirulence. To investigate the role of gE cytoplasmic tail sequences in the neuropathogenesis of BHV-5 in rabbits, we constructed a BHV-5gE recombinant virus with a short residual cytoplasmic domain lacking the YXXL motifs and the acidic (BHV-5gEAm480). In vitro, BHV-5gEAm480 produced on the average smaller plaques, compared with wild-type BHV-5, but it produced on the average substantially larger plaques than the gE ORF-deleted BHV-5. The truncated gE was not phosphorylated, and was not endocytosed from the cell surface. Importantly, the truncated gE was not incorporated into enveloped infectious virions, but its glycosylation and interaction with gI were not affected. In a rabbit model of infection, the BHV-5gEAm480 remained highly virulent, while the gE-null virus was avirulent. The gEAm480 mutant virus invaded most of the central nervous system (CNS) structures that are invaded by the wild-type BHV-5. The number of neurons infected by BHV-5gEAm480 was very similar to the number infected by BHV-5 wild-type and gEAm480-rescued viruses. Collectively, the results suggest that gE functions in transsynaptic transmission of BHV-5 and neurovirulence without being a structural component of the virion particle.
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
authors.forename: A
authors.initials: A
authors.lastname: Al-Mubarak
authors.forename: J
authors.initials: J
authors.lastname: Simon
authors.forename: C
authors.initials: C
authors.lastname: Coats
authors.forename: J D
authors.initials: JD
authors.lastname: Okemba
authors.forename: M D
authors.initials: MD
authors.lastname: Burton
authors.forename: S I
authors.initials: SI
authors.lastname: Chowdhury
mesh_terms: D000818:Animals; D001921:Brain / Q000821:virology; D002417:Cattle; D002460:Cell Line; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000821:virology; D004705:Endocytosis; D006566:Herpesviridae Infections / Q000821:virology; D025881:Herpesvirus 5, Bovine / Q000235:genetics / Q000472:pathogenicity*; D008590:Meningoencephalitis / Q000821:virology; D010766:Phosphorylation; D011485:Protein Binding; D011817:Rabbits; D017384:Sequence Deletion; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology*; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000032:analysis; D014771:Virion / Q000737:chemistry; D014774:Virulence
chemical_list: D014759:Viral Envelope Proteins; D014764:Viral Proteins; C414993:glycoprotein E, bovine herpesvirus type 5