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Macrophage-Mediated Optic Neuritis Induced by Retrograde Axonal Transport of Spike Gene Recombinant Mouse Hepatitis Virus
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-ho...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Association of Neuropathologists, Inc.
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110774/ https://www.ncbi.nlm.nih.gov/pubmed/21572336 http://dx.doi.org/10.1097/NEN.0b013e31821da499 |
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author | Shindler, Kenneth S. Chatterjee, Dhriti Biswas, Kaushiki Goyal, Ashish Dutt, Mahasweta Nassrallah, Mayssa Khan, Reas S. Das Sarma, Jayasri |
author_facet | Shindler, Kenneth S. Chatterjee, Dhriti Biswas, Kaushiki Goyal, Ashish Dutt, Mahasweta Nassrallah, Mayssa Khan, Reas S. Das Sarma, Jayasri |
author_sort | Shindler, Kenneth S. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3110774 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | American Association of Neuropathologists, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-31107742012-06-01 Macrophage-Mediated Optic Neuritis Induced by Retrograde Axonal Transport of Spike Gene Recombinant Mouse Hepatitis Virus Shindler, Kenneth S. Chatterjee, Dhriti Biswas, Kaushiki Goyal, Ashish Dutt, Mahasweta Nassrallah, Mayssa Khan, Reas S. Das Sarma, Jayasri J Neuropathol Exp Neurol Original Articles 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. American Association of Neuropathologists, Inc. 2011-06 2011-06 /pmc/articles/PMC3110774/ /pubmed/21572336 http://dx.doi.org/10.1097/NEN.0b013e31821da499 Text en Copyright © 2011 by the American Association of Neuropathologists, Inc. This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections. |
spellingShingle | Original Articles Shindler, Kenneth S. Chatterjee, Dhriti Biswas, Kaushiki Goyal, Ashish Dutt, Mahasweta Nassrallah, Mayssa Khan, Reas S. Das Sarma, Jayasri Macrophage-Mediated Optic Neuritis Induced by Retrograde Axonal Transport of Spike Gene Recombinant Mouse Hepatitis Virus |
title | Macrophage-Mediated Optic Neuritis Induced by Retrograde Axonal Transport of Spike Gene Recombinant Mouse Hepatitis Virus |
title_full | Macrophage-Mediated Optic Neuritis Induced by Retrograde Axonal Transport of Spike Gene Recombinant Mouse Hepatitis Virus |
title_fullStr | Macrophage-Mediated Optic Neuritis Induced by Retrograde Axonal Transport of Spike Gene Recombinant Mouse Hepatitis Virus |
title_full_unstemmed | Macrophage-Mediated Optic Neuritis Induced by Retrograde Axonal Transport of Spike Gene Recombinant Mouse Hepatitis Virus |
title_short | Macrophage-Mediated Optic Neuritis Induced by Retrograde Axonal Transport of Spike Gene Recombinant Mouse Hepatitis Virus |
title_sort | macrophage-mediated optic neuritis induced by retrograde axonal transport of spike gene recombinant mouse hepatitis virus |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110774/ https://www.ncbi.nlm.nih.gov/pubmed/21572336 http://dx.doi.org/10.1097/NEN.0b013e31821da499 |
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