Efficient axonal localization of alphaherpesvirus structural proteins in cultured sympathetic neurons requires viral glycoprotein E.
Pseudorabies virus (PRV) glycoprotein E (gE) is a type I viral membrane protein that facilitates the anterograde spread of viral infection from the peripheral nervous system to the brain. In animal models, a gE-null mutant infection spreads inefficiently from presynaptic neurons to postsynaptic neurons (anterograde spread of infection). However, the retrograde spread of infection from post- to presynaptic neurons remains unaffected. Here we show that gE is required for wild-type localization of viral structural proteins in axons of infected neurons. During a gE-null PRV infection, a subset of viral glycoproteins, capsids, and tegument proteins enter and localize to the axon inefficiently. This defect is most obvious in the distal axon and growth cones. However, axonal entry and localization of other viral membrane proteins and endogenous cellular proteins remains unaffected. Neurons infected with gE-null mutants produce wild-type levels of viral structural proteins and infectious virions in the cell body. Our results indicate that reduced axonal targeting of viral structural proteins is a compelling explanation for the lack of anterograde spread in neural circuits following infection by a gE-null mutant.
Ch'ng
T H
TH
Dept. of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Enquist
L W
LW
D000818:Animals; D001370:Axonal Transport; D036022:Capsid Proteins / Q000378:metabolism; D002478:Cells, Cultured; D021381:Protein Transport; D051381:Rats; D015398:Signal Transduction; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000821:virology*; D014759:Viral Envelope Proteins / Q000502:physiology*; D015678:Viral Structural Proteins / Q000378:metabolism*
D036022:Capsid Proteins; D014759:Viral Envelope Proteins; D015678:Viral Structural Proteins; C089580:glycoprotein E, Suid herpesvirus 1