title: Direct transfer of viral and cellular proteins from varicella-zoster virus-infected non-neuronal cells to human axons.
abstract: Varicella Zoster Virus (VZV), the alphaherpesvirus that causes varicella upon primary infection and Herpes zoster (shingles) following reactivation in latently infected neurons, is known to be fusogenic. It forms polynuclear syncytia in culture, in varicella skin lesions and in infected fetal human ganglia xenografted to mice. After axonal infection using VZV expressing green fluorescent protein (GFP) in compartmentalized microfluidic cultures there is diffuse filling of axons with GFP as well as punctate fluorescence corresponding to capsids. Use of viruses with fluorescent fusions to VZV proteins reveals that both proteins encoded by VZV genes and those of the infecting cell are transferred in bulk from infecting non-neuronal cells to axons. Similar transfer of protein to axons was observed following cell associated HSV1 infection. Fluorescence recovery after photobleaching (FRAP) experiments provide evidence that this transfer is by diffusion of proteins from the infecting cells into axons. Time-lapse movies and immunocytochemical experiments in co-cultures demonstrate that non-neuronal cells fuse with neuronal somata and proteins from both cell types are present in the syncytia formed. The fusogenic nature of VZV therefore may enable not only conventional entry of virions and capsids into axonal endings in the skin by classical entry mechanisms, but also by cytoplasmic fusion that permits viral protein transfer to neurons in bulk.
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Sergei
authors.initials: S
authors.lastname: Grigoryan
authors.affiliation: Departments of Ophthalmology, Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Yee
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Glick
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Doron
authors.initials: D
authors.lastname: Gerber
authors.affiliation: Department of Physics, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Eldad
authors.initials: E
authors.lastname: Kepten
authors.affiliation: Department of Physics, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Garini
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America; SiNAPSE National University of Singapore, Singapore, Singapore.
authors.forename: In Hong
authors.initials: IH
authors.lastname: Yang
authors.affiliation: Departments of Ophthalmology, Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Kinchington
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Goldstein
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000821:virology*; D002460:Cell Line; D006562:Herpes Zoster / Q000378:metabolism*; D014645:Herpesvirus 3, Human / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D021381:Protein Transport; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D014764:Viral Proteins / Q000032:analysis / Q000378:metabolism*
chemical_list: D011506:Proteins; D014764:Viral Proteins