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
Hélène JacomyP J Talbot

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 ...Continue Reading

Citations

Jun 22, 2018·Journal of Virology·Mathieu DubéPierre J Talbot
May 18, 2020·Journal of Neurovirology·Ali SepehrinezhadSajad Sahab Negah
Aug 7, 2020·Médecine sciences : M/S·Sara Salinas, Yannick Simonin
Sep 15, 2020·Journal of Alzheimer's Disease : JAD·Vicky YamamotoBabak Kateb
Jul 14, 2020·Frontiers in Neurology·Mohamed KhatebMaryam Muqary
Aug 6, 2020·International Journal of Molecular Sciences·Manuela PennisiRita Bella
Jan 20, 2021·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Júlia Leão Batista Simões, Margarete Dulce Bagatini
Dec 15, 2020·Neurology. Neuroimmunology and Neuroinflammation·Marta BodroRaquel Sánchez-Valle
Oct 23, 2020·Neuroscience and Biobehavioral Reviews·Jingman HuChuansheng Zhao
Apr 13, 2021·The FEBS Journal·Avindra Nath, Tory P Johnson

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