Herpes simplex virus type 1 glycoprotein E mediates retrograde spread from epithelial cells to neurites.
In animal models of infection, glycoprotein E (gE) is required for efficient herpes simplex virus type 1 (HSV-1) spread from the inoculation site to the cell bodies of innervating neurons (retrograde direction). Retrograde spread in vivo is a multistep process, in that HSV-1 first spreads between epithelial cells at the inoculation site, then infects neurites, and finally travels by retrograde axonal transport to the neuron cell body. To better understand the role of gE in retrograde spread, we used a compartmentalized neuron culture system, in which neurons were infected in the presence or absence of epithelial cells. We found that gE-deleted HSV-1 (NS-gEnull) retained retrograde axonal transport activity when added directly to neurites, in contrast to the retrograde spread defect of this virus in animals. To better mimic the in vivo milieu, we overlaid neurites with epithelial cells prior to infection. In this modified system, virus infects epithelial cells and then spreads to neurites, revealing a 100-fold retrograde spread defect for NS-gEnull. We measured the retrograde spread defect of NS-gEnull from a variety of epithelial cell lines and found that the magnitude of the spread defect from epithelial cells to neurons correlated with epithelial cell plaque size defect, indicating that gE plays a similar role in both types of spread. Therefore, gE-mediated spread between epithelial cells and neurites likely explains the retrograde spread defect of gE-deleted HSV-1 in vivo.
McGraw
Helen M
HM
Division of Infectious Diseases, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6073, USA.
Friedman
Harvey M
HM
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D004847:Epithelial Cells / Q000821:virology*; D006561:Herpes Simplex / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D006801:Humans; D051379:Mice; D016501:Neurites / Q000821:virology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism*; D010948:Viral Plaque Assay
D014759:Viral Envelope Proteins; C044768:glycoprotein E, herpes simplex virus type 1