Related Experiment Video
Updated: Jun 2, 2026
Viral Tracing of Genetically Defined Neural Circuitry
Published on: October 17, 2012
Macrophage-mediated optic neuritis induced by retrograde axonal transport of spike gene recombinant mouse hepatitis
Kenneth S Shindler1, Dhriti Chatterjee, Kaushiki Biswas
1Scheie Eye Institute, University of Pennsylvania, Philadelphia, USA.
Abstract:
After intracranial inoculation, neurovirulent mouse hepatitis virus (MHV) strains induce acute inflammation, demyelination, and axonal loss in the central nervous system. Prior studies using recombinant MHV strains that differ only in the spike gene, which encodes a glycoprotein involved in virus-host cell attachment, demonstrated that spike mediates anterograde axonal transport of virus to the spinal cord. A demyelinating MHV strain induces optic neuritis, but whether this is due to the retrograde axonal transport of viral particles to the retina or due to traumatic disruption of retinal ganglion cell axons during intracranial inoculation is not known. Using recombinant isogenic MHV strains, we examined the ability of recombinant MHV to induce optic neuritis by retrograde spread from the brain through the optic nerve into the eye after intracranial inoculation. Recombinant demyelinating MHV induced macrophage infiltration of optic nerves, demyelination, and axonal loss, whereas optic neuritis and axonal injury were minimal in mice infected with the nondemyelinating MHV strain that differs in the spike gene. Thus, optic neuritis was dependent on a spike glycoprotein-mediated mechanism of viral antigen transport along retinal ganglion cell axons. These data indicate that MHV spreads by retrograde axonal transport to the eye and that targeting spike protein interactions with axonal transport machinery is a potential therapeutic strategy for central nervous system viral infections and associated diseases.
Insights
Mouse hepatitis virus (MHV) spreads to the eye via retrograde axonal transport, causing optic neuritis. Targeting the spike protein may offer a therapeutic strategy for central nervous system viral diseases.
Area of Science:
- Neurovirology
- Central Nervous System (CNS) Infections
- Demyelinating Diseases
Background:
- Neurovirulent mouse hepatitis virus (MHV) strains cause inflammation, demyelination, and axonal loss in the CNS.
- Previous studies implicated the MHV spike gene in anterograde axonal transport to the spinal cord.
- The mechanism of MHV-induced optic neuritis, specifically retrograde spread to the retina, remained unclear.
Purpose of the Study:
- To investigate the role of retrograde axonal transport in MHV-induced optic neuritis.
- To determine if the MHV spike glycoprotein mediates viral spread to the eye via retinal ganglion cell axons.
Main Methods:
- Utilized recombinant isogenic MHV strains differing in the spike gene.
- Administered intracranial inoculation to mice.
- Assessed optic nerve and retinal pathology, including inflammation, demyelination, and axonal injury.
Main Results:
- Recombinant demyelinating MHV induced significant macrophage infiltration, demyelination, and axonal loss in optic nerves.
- Optic neuritis and axonal injury were minimal in mice infected with the nondemyelinating MHV strain.
- MHV-induced optic neuritis was dependent on spike glycoprotein-mediated transport along retinal ganglion cell axons.
Conclusions:
- MHV spreads to the eye through retrograde axonal transport within the optic nerve.
- The MHV spike glycoprotein plays a critical role in this retrograde spread.
- Targeting spike protein interactions with axonal transport machinery presents a potential therapeutic avenue for CNS viral infections and associated optic neuropathies.
More Related Videos
Related Concept Videos
01:28Rabies
01:26Encephalitis ll: Pathophysiology