title: A single viral gene determines lethal cross-species neurovirulence of baboon herpesvirus HVP2.
abstract: Alpha-herpesviruses can produce more severe infections in non-natural host species than in their natural host. Isolates of the baboon alpha-herpesvirus Papiine herpesvirus 2 (HVP2) are either very neurovirulent in mice (subtype nv) or non-virulent (subtype ap), but no such difference is evident in the natural baboon host. Comparative genome sequencing was used to identify subtype-specific sequence differences (SSDs) between HVP2nv and HVP2ap isolates. Some genes were identified that despite exhibiting sequence variation among isolates did not have any SSDs, while other genes had comparatively high levels of SSDs. Construction of genomic recombinants between HVP2nv and HVP2ap isolates mapped the mouse neurovirulence determinant to within three genes. Construction of gene-specific recombinants demonstrated that the UL39 ORF is responsible for determining the lethal neurovirulence phenotype of HVP2 in mice. These results demonstrate that differences in a single viral gene can determine the severity of herpesvirus infection in a non-natural host species.
authors.affiliation: Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, United States.
authors.forename: Darla
authors.initials: D
authors.lastname: Black
authors.affiliation: Center for Frontier Life Sciences, Division of Comparative Medicine, Nagasaki University, Nagasaki, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ohsawa
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Canadian Science Centre for Human and Animal Health, Winnipeg, Canada R3E 3P6.
authors.forename: Shaun
authors.initials: S
authors.lastname: Tyler
authors.affiliation: Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, United States.
authors.forename: Lara
authors.initials: L
authors.lastname: Maxwell
authors.affiliation: Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, United States. Electronic address: r.eberle@okstate.edu.
authors.forename: R
authors.initials: R
authors.lastname: Eberle
mesh_terms: D000818:Animals; D006561:Herpes Simplex / Q000662:veterinary* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008992:Monkey Diseases / Q000821:virology*; D010215:Papio; D012264:Ribonucleotide Reductases / Q000235:genetics / Q000378:metabolism*; D018139:Simplexvirus / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D013045:Species Specificity; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D012264:Ribonucleotide Reductases
keywords: HVP2; Herpesvirus; Neurovirulence; Zoonoses