title: Functional hierarchy of herpes simplex virus type-1 membrane proteins in corneal infection and virus transmission to ganglionic neurons.
abstract: OBJECTIVE
  To determine the relative importance of viral glycoproteins gK, gM, gE and the membrane protein UL11 in infection of mouse corneas and ganglionic neurons.
  
  
  METHODS
  Mouse eyes were scarified and infected with herpes simplex virus (HSV)-1(F), gE-null, gM-null, gK-null, or UL11-null viruses. Clinical signs of ocular disease were monitored daily. Virus shedding was determined at 24, 48 and 72 h post infection. Viral DNA within trigeminal ganglia (TG) was quantified by quantitative PCR at 30 d post infection.
  
  
  RESULTS
  The gE-null virus replicated as efficiently as the parental virus and formed viral plaques approximately half-the-size in comparison with the HSV-1(F) wild-type virus. The UL11-null and gM-null viruses replicated approximately one log less efficiently than the wild-type virus, and formed plaques that were on average one-third the size and one-half the size of the wild-type virus, respectively. The gK-null virus replicated more than 3-logs less efficiently than the wild-type virus and formed very small plaques (5-10 cells). Mice infected with the wild-type virus exhibited mild clinical ocular symptoms, while mice infected with the mutant viruses did not show any significant ocular changes. The wild-type virus produced the highest virus shedding post infection followed by the gM-null, gE-null and UL11-null viruses, while no gK-null virus was detected at any time point. All TG collected from mice infected with the wild-type virus and 6-of-10 of TG retrieved from mice infected with the UL11-null virus contained high numbers of viral genomes. The gE-null and gM-null-infected ganglia contained moderate-to-low number of viral genomes in 4-of-10 and 2-of-10 mice, respectively. No viral genomes were detected in ganglionic tissues obtained from gK-null eye infections.
  
  
  CONCLUSIONS
  The results show that gK plays the most important role among gM, gE and UL11 in corneal and ganglionic infection in the mouse eye model.
authors.affiliation: Division of Biotechnology & Molecular Medicine, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University , Baton Rouge, LA , USA.
authors.forename: In-Joong
authors.initials: IJ
authors.lastname: Kim
authors.forename: Ahmad A
authors.initials: AA
authors.lastname: Saied
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Chouljenko
authors.forename: Ramesh
authors.initials: R
authors.lastname: Subramanian
authors.forename: Konstantin G
authors.initials: KG
authors.lastname: Kousoulas
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D022202:Chromosomes, Artificial, Bacterial; D003315:Cornea / Q000294:innervation* / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D004195:Disease Models, Animal; D018259:Herpesvirus 1, Human / Q000502:physiology*; D016849:Keratitis, Herpetic / Q000821:virology*; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D060888:Real-Time Polymerase Chain Reaction; D012668:Trigeminal Ganglion / Q000821:virology*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000502:physiology; D014763:Viral Matrix Proteins / Q000502:physiology*; D014764:Viral Proteins / Q000502:physiology; D015678:Viral Structural Proteins / Q000502:physiology; D014779:Virus Replication; D017201:Virus Shedding / Q000502:physiology
chemical_list: D004279:DNA, Viral; D008562:Membrane Glycoproteins; C081689:UL10 protein, Human herpesvirus 1; C073414:UL11 protein, herpesviridae; C072448:UL53 protein, Human herpesvirus 1; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D015678:Viral Structural Proteins; C044768:glycoprotein E, herpes simplex virus type 1
keywords: UL11; gE; gK; gM; herpes simplex virus; neuroinvasion; ocular infection