title: Dynamic ubiquitination drives herpesvirus neuroinvasion.
abstract: Neuroinvasive herpesviruses display a remarkable propensity to enter the nervous system of healthy individuals in the absence of obvious trauma at the site of inoculation. We document a repurposing of cellular ubiquitin during infection to switch the virus between two invasive states. The states act sequentially to defeat consecutive host barriers of the peripheral nervous system and together promote the potent neuroinvasive phenotype. The first state directs virus access to nerve endings in peripheral tissue, whereas the second delivers virus particles within nerve fibers to the neural ganglia. Mutant viruses locked in either state remain competent to overcome the corresponding barrier but fail to invade the nervous system. The herpesvirus "ubiquitin switch" may explain the unusual ability of these viruses to routinely enter the nervous system and, as a consequence, their prevalence in human and veterinary hosts.
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611;
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Huffmaster
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, NE 68583;
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Sollars
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611;
authors.forename: Alexsia L
authors.initials: AL
authors.lastname: Richards
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, NE 68583; Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE 68198.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Pickard
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611; g-smith3@northwestern.edu.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Smith
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D006561:Herpes Simplex / Q000235:genetics / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D006801:Humans; D009474:Neurons / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D054875:Ubiquitination; D014709:Vero Cells
keywords: HSV-1; PRV; herpesvirus; neuroinvasion; ubiquitin