Linked Life Data

20642316

Source:http://linkedlifedata.com/resource/pubmed/id/20642316

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-8-2
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1538-2443
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
279-93
pubmed:dateRevised
2011-3-29
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Mutations in the spike glycoprotein of human coronavirus OC43 modulate disease in BALB/c mice from encephalitis to flaccid paralysis and demyelination.
pubmed:affiliation
Laboratory of Neuroimmunovirology, INRS-Institute Armand-Frappier, Laval, Québec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't