title: Role of the virion host shutoff protein in neurovirulence of monkey B virus (Macacine herpesvirus 1).
abstract: Monkey B virus (Macacine herpesvirus 1; BV) is noted for its extreme neurovirulence in humans. Since the vhs protein encoded by the UL41 gene has been shown to be a neurovirulence factor in the related human herpes simplex viruses, the role of the UL41 gene in BV neurovirulence was investigated. BV mutants were constructed that lacked the entire UL41 ORF (Δ41) or had the RNase active site mutated (Δ41A). Neither mutant shut off host protein synthesis, degraded β-actin mRNA, or prevented an IFN-β response, indicating that the vhs protein and its RNase activity are both necessary for these activities. Replication of both mutants in primary mouse cells was impaired and they exhibited a prolonged disease course in mice. Whereas Δ41 infected mice were euthanized for symptoms related to central nervous system (CNS) infection, Δ41A infected mice were euthanized primarily for symptoms of autonomic nervous system dysfunction. While neuroinvasiveness was not affected, lesions in the CNS were more limited in size, anatomical distribution, and severity than for wild-type virus. These results indicate that the vhs protein affects the general replicative efficiency of BV in vivo rather than being a specific neurovirulence factor critical for invasion of or preferential replication in the CNS.
authors.affiliation: Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Oklahoma, 74078, USA.
authors.forename: Darla
authors.initials: D
authors.lastname: Black
authors.forename: Jerry
authors.initials: J
authors.lastname: Ritchey
authors.forename: Mark
authors.initials: M
authors.lastname: Payton
authors.forename: Richard
authors.initials: R
authors.lastname: Eberle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002490:Central Nervous System / Q000473:pathology; D004195:Disease Models, Animal; D017353:Gene Deletion; D006566:Herpesviridae Infections / Q000473:pathology*; D006568:Herpesvirus 1, Cercopithecine / Q000254:growth & development*; D006651:Histocytochemistry; D008807:Mice, Inbred BALB C; D008853:Microscopy; D008969:Molecular Sequence Data; D009187:Myelitis / Q000473:pathology*; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism*; D019562:Viral Load; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014764:Viral Proteins; D037521:Virulence Factors; C070722:virion host shutoff protein, Simplexvirus; D012260:Ribonucleases