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Journal of Virology, October 2000, p. 8913-8921, Vol. 74, No. 19
Laboratory of Neuroimmunovirology, Human
Health Research Center, INRS-Armand-Frappier Institute, University
of Quebec, Laval, Québec, Canada H7V 1B71;
Department of Pharmacology, University of Sherbrooke,
Sherbrooke, Québec, Canada J1H 5N42; and
NeuroResource, Institute of Neurology, University College
London, London WC1N 1PJ, England3
Received 17 February 2000/Accepted 10 July 2000
Human coronaviruses (HCoV) cause common colds but can also infect
neural cell cultures. To provide definitive experimental evidence for
the neurotropism and neuroinvasion of HCoV and its possible association
with multiple sclerosis (MS), we have performed an extensive search and
characterization of HCoV RNA in a large panel of human brain autopsy
samples. Very stringent reverse transcription-PCR with two primer pairs
for both viral strains (229E and OC43), combined with Southern
hybridization, was performed on samples from 90 coded donors with
various neurological diseases (39 with MS and 26 with other
neurological diseases) or normal controls (25 patients). We report that
44% (40 of 90) of donors were positive for 229E and that 23% (21 of
90) were positive for OC43. A statistically significant higher
prevalence of OC43 in MS patients (35.9%; 14 of 39) than in controls
(13.7%; 7 of 51) was observed. Sequencing of nucleocapsid protein (N)
gene amplicons revealed point mutations in OC43, some consistently
found in three MS patient brains and one normal control but never
observed in laboratory viruses. In situ hybridization confirmed the
presence of viral RNA in brain parenchyma, outside blood vessels. The
presence of HCoV in human brains is consistent with neuroinvasion by
these respiratory pathogens. Further studies are needed to distinguish
between opportunistic and disease-associated viral presence in human brains.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Neuroinvasion by Human Respiratory
Coronaviruses

*
Corresponding author. Mailing address: Centre de
Recherche en Santé Humaine, INRS-Institut Armand-Frappier, 531 boulevard des Prairies, Laval, Québec, Canada H7V 1B7. Phone:
(450) 686-5515. Fax: (450) 686-5566 or -5531. E-mail:
Pierre.Talbot{at}inrs-iaf.uquebec.ca.
Present address: Neuropharmacology Department, The Scripps Research
Institute, La Jolla, CA 92037.
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