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D. A. Cortez, A. Sucher, J. H. LaVail; HSV Viral Envelope Proteins Partition With Lipid Rafts in Infected Retinal Ganglion Cell Axons. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3166.
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Herpes simplex virus type 1 (HSV) is responsible for recurrent scarring of the corneal epithelium in ocular herpetic keratitis, a common cause of blindness. HSV envelope glycoproteins are essential for cell-cell spread of infection from trigeminal axons to corneal cells. What has been lacking is details of how newly made envelope proteins are transported within axons. By analogy to the transport of synaptic membrane precursors, lipid raft membranes may also support the transport of viral glycoproteins. We have tested the hypothesis that HSV glycoproteins are transported in association with lipid raft membranes in infected retinal axons in vivo.
Murine retinal ganglion cells were infected with a wild-type (wt) virus, and after 24 hrs the mice were given Valacyclovir to pulse infect the neurons. The optic pathways were dissected 5 days postinfection, and the tissues were processed for Western blotting using antibodies to gB, gC and gD. Additional animals were infected and treated as above, but the optic pathways were dissected and prepared in an Optiprep flotation assay to separate detergent-resistant membranes (DRM) and detergent-soluble membranes (DSM). We used GM1 and caveolin as control proteins for DRM and transferrin receptor as a control for DSM.
By 5 days postinfection all three glycoproteins were transported to the OT. However, the transport of gD appeared to be more efficient than that of gC or gB. In preliminary studies all of the tested glycoproteins, (gB, gC, and gD) as well as GM1 and caveolin were present in the DRM fractions. We also found gB, gC and gD in the DSM fraction. Transferrin receptor was found principally in the DSM fraction.
By five days after infection the three glycoproteins had been transported to the most distal portion of the retinal axons. The three envelope glycoproteins associated with the lipid raft membrane fraction. Further experiments to define host membrane components that associate with transported viral glycoproteins will be essential to understanding the intracellular localization and mechanisms of transport.
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