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Mutations in the spike glycoprotein of human coronavirus OC43 modulate disease in BALB/c mice from encephalitis to flaccid paralysis and demyelination.
J Neurovirol. 2010 Jul; 16(4):279-93.JN

Abstract

The etiology of most neurodegenerative diseases of the central nervous system remains unknown and likely involves a combination of genetic susceptibility and environmental triggering factors. Given that exposure to numerous infectious pathogens occurs during childhood, and that some viral infections can lead to neurodegeneration and demyelination, it is conceivable that some viruses may act as triggering factors in neuropathogenesis. We have previously shown that the prototype OC43 strain of the common cold-associated human respiratory coronavirus has the capacity to infect human neuronal and glial cells and does persist in human brains. Moreover, it has neuroinvasive properties in susceptible BALB/c mice, where it leads to a chronic encephalitis with accompanying disabilities. Here, we show that mutations in the viral spike glycoprotein, reproducibly acquired during viral persistence in human neural cell cultures, led to a drastically modified virus-induced neuropathology in BALB/c mice, characterized by flaccid paralysis and demyelination. Even though infection by both mutated and wild-type viruses led to neuroinflammation, the modified neuropathogenesis induced by the mutated virus was associated with increased viral spread and significantly more CD4+ and CD8+ T-lymphocyte infiltration into the central nervous system, as well as significantly increased levels of the proinflammatory cytokine interleukin (IL)-6 and the chemokine CCL2 (monocyte chemoattractant protein [MCP]-1). Moreover, recombinant virus harboring the S glycoprotein mutations retained its neurotropism, productively infecting neurons. Therefore, interaction of a human respiratory coronavirus with the central nervous system may modulate virus and host factors resulting in a modified neuropathogenesis in genetically susceptible individuals.

Authors+Show Affiliations

Laboratory of Neuroimmunovirology, INRS-Institute Armand-Frappier, Laval, Québec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20642316

Citation

Jacomy, Hélène, et al. "Mutations in the Spike Glycoprotein of Human Coronavirus OC43 Modulate Disease in BALB/c Mice From Encephalitis to Flaccid Paralysis and Demyelination." Journal of Neurovirology, vol. 16, no. 4, 2010, pp. 279-93.
Jacomy H, St-Jean JR, Brison E, et al. Mutations in the spike glycoprotein of human coronavirus OC43 modulate disease in BALB/c mice from encephalitis to flaccid paralysis and demyelination. J Neurovirol. 2010;16(4):279-93.
Jacomy, H., St-Jean, J. R., Brison, E., Marceau, G., Desforges, M., & Talbot, P. J. (2010). Mutations in the spike glycoprotein of human coronavirus OC43 modulate disease in BALB/c mice from encephalitis to flaccid paralysis and demyelination. Journal of Neurovirology, 16(4), 279-93. https://doi.org/10.3109/13550284.2010.497806
Jacomy H, et al. Mutations in the Spike Glycoprotein of Human Coronavirus OC43 Modulate Disease in BALB/c Mice From Encephalitis to Flaccid Paralysis and Demyelination. J Neurovirol. 2010;16(4):279-93. PubMed PMID: 20642316.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutations in the spike glycoprotein of human coronavirus OC43 modulate disease in BALB/c mice from encephalitis to flaccid paralysis and demyelination. AU - Jacomy,Hélène, AU - St-Jean,Julien R, AU - Brison,Elodie, AU - Marceau,Gabriel, AU - Desforges,Marc, AU - Talbot,Pierre J, PY - 2010/7/21/entrez PY - 2010/7/21/pubmed PY - 2010/11/16/medline SP - 279 EP - 93 JF - Journal of neurovirology JO - J Neurovirol VL - 16 IS - 4 N2 - The etiology of most neurodegenerative diseases of the central nervous system remains unknown and likely involves a combination of genetic susceptibility and environmental triggering factors. Given that exposure to numerous infectious pathogens occurs during childhood, and that some viral infections can lead to neurodegeneration and demyelination, it is conceivable that some viruses may act as triggering factors in neuropathogenesis. We have previously shown that the prototype OC43 strain of the common cold-associated human respiratory coronavirus has the capacity to infect human neuronal and glial cells and does persist in human brains. Moreover, it has neuroinvasive properties in susceptible BALB/c mice, where it leads to a chronic encephalitis with accompanying disabilities. Here, we show that mutations in the viral spike glycoprotein, reproducibly acquired during viral persistence in human neural cell cultures, led to a drastically modified virus-induced neuropathology in BALB/c mice, characterized by flaccid paralysis and demyelination. Even though infection by both mutated and wild-type viruses led to neuroinflammation, the modified neuropathogenesis induced by the mutated virus was associated with increased viral spread and significantly more CD4+ and CD8+ T-lymphocyte infiltration into the central nervous system, as well as significantly increased levels of the proinflammatory cytokine interleukin (IL)-6 and the chemokine CCL2 (monocyte chemoattractant protein [MCP]-1). Moreover, recombinant virus harboring the S glycoprotein mutations retained its neurotropism, productively infecting neurons. Therefore, interaction of a human respiratory coronavirus with the central nervous system may modulate virus and host factors resulting in a modified neuropathogenesis in genetically susceptible individuals. SN - 1538-2443 UR - https://www.unboundmedicine.com/medline/citation/20642316/Mutations_in_the_spike_glycoprotein_of_human_coronavirus_OC43_modulate_disease_in_BALB/c_mice_from_encephalitis_to_flaccid_paralysis_and_demyelination_ L2 - https://dx.doi.org/10.3109/13550284.2010.497806 DB - PRIME DP - Unbound Medicine ER -