Herpes simplex virus type 2 glycoprotein E is required for efficient virus spread from epithelial cells to neurons and for targeting viral proteins from the neuron cell body into axons.
The HSV-2 lifecycle involves virus spread in a circuit from the inoculation site to dorsal root ganglia and return. We evaluated the role of gE-2 in the virus lifecycle by deleting amino acids 124-495 (gE2-del virus). In the mouse retina infection model, gE2-del virus does not spread to nuclei in the brain, indicating a defect in anterograde (pre-synaptic to post-synaptic neurons) and retrograde (post-synaptic to pre-synaptic neurons) spread. Infection of neuronal cells in vitro demonstrates that gE-2 is required for targeting viral proteins from neuron cell bodies into axons, and for efficient virus spread from epithelial cells to axons. The mouse flank model confirms that gE2-del virus is defective in spread from epithelial cells to neurons. Therefore, we defined two steps in the virus lifecycle that involve gE-2, including efficient spread from epithelial cells to axons and targeting viral components from neuron cell bodies into axons.
Wang
Fushan
F
Division of Infectious Diseases, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6073, USA. fushanw18@hotmail.com
Zumbrun
Elizabeth E
EE
Huang
Jialing
J
Si
Huaxin
H
Makaroun
Lena
L
Friedman
Harvey M
HM
D000818:Animals; D001369:Axons / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000821:virology*; D005260:Female; D006561:Herpes Simplex / Q000503:physiopathology / Q000821:virology; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D015603:Keratinocytes / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000378:metabolism / Q000821:virology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000821:virology; D017384:Sequence Deletion; D014621:Vagina / Q000821:virology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D014759:Viral Envelope Proteins; D014764:Viral Proteins; C048621:glycoprotein E, herpes simplex-virus type 2