title: Herpes simplex virus type 1 mutants containing the KOS strain ICP34.5 gene in place of the McKrae ICP34.5 gene have McKrae-like spontaneous reactivation but non-McKrae-like virulence.
abstract: Herpes simplex virus type 1 (HSV-1) strain McKrae is neurovirulent in rabbits infected by the ocular route, causing fatal encephalitis in approximately 50% of the animals, and has a high-level spontaneous reactivation phenotype, with 10% of rabbit eyes containing reactivated virus at any given time. In contrast, HSV-1 strain KOS is completely avirulent (no rabbits die) and has a completely negative spontaneous reactivation phenotype. Mutations of the ICP34.5 gene can reduce the neurovirulence of HSV-1 strains McKrae and 17syn(+) by up to 100000-fold. ICP34.5 mutants also have reduced spontaneous reactivation phenotypes. To determine whether differences in the ICP34.5 gene might be involved in the reduced neurovirulence and spontaneous reactivation phenotypes of KOS compared with McKrae, we constructed chimeric viruses containing the KOS ICP34.5 gene in place of the McKrae ICP34.5 gene. Rabbits ocularly infected with the chimeric viruses had a high spontaneous reactivation phenotype indistinguishable from McKrae. In contrast, neurovirulence of the chimeric viruses was decreased compared with McKrae. Thus, one or more 'defects' in the KOS ICP34.5 gene appeared to be at least partially responsible for the reduced neurovirulence of KOS compared with McKrae. However, there appeared to be no 'defect' in the KOS ICP34.5 function required for efficient spontaneous reactivation.
authors.affiliation: Department of Ophthalmology, School of Medicine, University of California Irvine, Medical Center, Building 55, Room 204, Orange, CA 92868, USA1.
authors.forename: Guey-Chuen
authors.initials: GC
authors.lastname: Perng
authors.affiliation: Department of Ophthalmology, School of Medicine, University of California Irvine, Medical Center, Building 55, Room 204, Orange, CA 92868, USA1.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Mott
authors.affiliation: Department of Ophthalmology, School of Medicine, University of California Irvine, Medical Center, Building 55, Room 204, Orange, CA 92868, USA1.
authors.forename: Nelson
authors.initials: N
authors.lastname: Osorio
authors.affiliation: Department of Ophthalmology, School of Medicine, University of California Irvine, Medical Center, Building 55, Room 204, Orange, CA 92868, USA1.
authors.forename: Ada
authors.initials: A
authors.lastname: Yukht
authors.affiliation: Department of Ophthalmology, School of Medicine, University of California Irvine, Medical Center, Building 55, Room 204, Orange, CA 92868, USA1.
authors.forename: Susan
authors.initials: S
authors.lastname: Salina
authors.affiliation: Department of Ophthalmology, School of Medicine, University of California Irvine, Medical Center, Building 55, Room 204, Orange, CA 92868, USA1.
authors.forename: Quynh-Hoa
authors.initials: QH
authors.lastname: Nguyen
authors.affiliation: Department of Ophthalmology, School of Medicine, University of California Irvine, Medical Center, Building 55, Room 204, Orange, CA 92868, USA1.
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Nesburn
authors.affiliation: Department of Ophthalmology, School of Medicine, University of California Irvine, Medical Center, Building 55, Room 204, Orange, CA 92868, USA1.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Wechsler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018792:Encephalitis, Viral / Q000503:physiopathology / Q000821:virology*; D005123:Eye / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D016849:Keratitis, Herpetic / Q000503:physiopathology / Q000821:virology*; D008969:Molecular Sequence Data; D009154:Mutation; D011817:Rabbits; D017422:Sequence Analysis, DNA; D014764:Viral Proteins / Q000235:genetics*; D014774:Virulence; D014775:Virus Activation; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D014764:Viral Proteins; C066469:gamma 34.5 protein, Human herpesvirus 1