title: Corneal replication is an interferon response-independent bottleneck for virulence of herpes simplex virus 1 in the absence of virion host shutoff.
abstract: Herpes simplex viruses lacking the virion host shutoff function (Δvhs) are avirulent and hypersensitive to type I and type II interferon (IFN). In this study, we demonstrate that even in the absence of IFN responses in AG129 (IFN-αβγR(-/-)) mice, Δvhs remains highly attenuated via corneal infection but is fully virulent via intracranial infection. The data demonstrate that the interferon-independent inherent replication defect of Δvhs has a significant impact upon peripheral replication and neuroinvasion.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Tracy Jo
authors.initials: TJ
authors.lastname: Pasieka
authors.forename: Vineet D
authors.initials: VD
authors.lastname: Menachery
authors.forename: Pamela C
authors.initials: PC
authors.lastname: Rosato
authors.forename: David A
authors.initials: DA
authors.lastname: Leib
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000821:virology; D003315:Cornea / Q000473:pathology / Q000821:virology*; D003713:Dendritic Cells / Q000821:virology; D018259:Herpesvirus 1, Human / Q000472:pathogenicity* / Q000502:physiology; D007370:Interferon Type I / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D016849:Keratitis, Herpetic / Q000821:virology*; D051379:Mice; D008822:Mice, Transgenic; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D007370:Interferon Type I; D014764:Viral Proteins; C070722:virion host shutoff protein, Simplexvirus; D007371:Interferon-gamma; D012260:Ribonucleases