title: Anterograde spread of herpes simplex virus type 1 requires glycoprotein E and glycoprotein I but not Us9.
abstract: Anterograde neuronal spread (i.e., spread from the neuron cell body toward the axon terminus) is a critical component of the alphaherpesvirus life cycle. Three viral proteins, gE, gI, and Us9, have been implicated in alphaherpesvirus anterograde spread in several animal models and neuron culture systems. We sought to better define the roles of gE, gI, and Us9 in herpes simplex virus type 1 (HSV-1) anterograde spread using a compartmentalized primary neuron culture system. We found that no anterograde spread occurred in the absence of gE or gI, indicating that these proteins are essential for HSV-1 anterograde spread. However, we did detect anterograde spread in the absence of Us9 using two independent Us9-deleted viruses. We confirmed the Us9 finding in different murine models of neuronal spread. We examined viral transport into the optic nerve and spread to the brain after retinal infection; the production of zosteriform disease after flank inoculation; and viral spread to the spinal cord after flank inoculation. In all models, anterograde spread occurred in the absence of Us9, although in some cases at reduced levels. This finding contrasts with gE- and gI-deleted viruses, which displayed no anterograde spread in any animal model. Thus, gE and gI are essential for HSV-1 anterograde spread, while Us9 is dispensable.
authors: Division of Infectious Diseases, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6073, USA.
authors: Helen M
authors: HM
authors: McGraw
authors: Sita
authors: S
authors: Awasthi
authors: Jason A
authors: JA
authors: Wojcechowskyj
authors: Harvey M
authors: HM
authors: Friedman
mesh_terms: D000818:Animals; D001921:Brain / Q000821:virology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D018259:Herpesvirus 1, Human / Q000254:growth & development / Q000472:pathogenicity*; D047908:Intracellular Signaling Peptides and Proteins; D008074:Lipoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009474:Neurons / Q000821:virology; D009900:Optic Nerve / Q000821:virology; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D051381:Rats; D013116:Spinal Cord / Q000821:virology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology*; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*; D037521:Virulence Factors / Q000502:physiology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008074:Lipoproteins; D010750:Phosphoproteins; C109622:US9 protein, Human herpesvirus 1; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D037521:Virulence Factors; C044768:glycoprotein E, herpes simplex virus type 1; C064959:glycoprotein I, herpes simplex virus type 1