Direct transfer of viral and cellular proteins from varicella-zoster virus-infected non-neuronal cells to human axons

Sergei Grigoryan, Michael B. Yee, Yair Glick, Doron Gerber, Eldad Kepten, Yuval Garini, In Hong Yang, Paul R. Kinchington, Ronald S. Goldstein

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere0126081
JournalPloS one
Volume10
Issue number5
DOIs
StatePublished - May 14 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Grigoryan, S., Yee, M. B., Glick, Y., Gerber, D., Kepten, E., Garini, Y., Yang, I. H., Kinchington, P. R., & Goldstein, R. S. (2015). Direct transfer of viral and cellular proteins from varicella-zoster virus-infected non-neuronal cells to human axons. PloS one, 10(5), [e0126081]. https://doi.org/10.1371/journal.pone.0126081