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Journal of Virology, October 2000, p. 8913-8921, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Neuroinvasion by Human Respiratory Coronaviruses

Nathalie Arbour,1,dagger Robert Day,2 Jia Newcombe,3 and Pierre J. Talbot1,*

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.

* 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.

dagger Present address: Neuropharmacology Department, The Scripps Research Institute, La Jolla, CA 92037.

Journal of Virology, October 2000, p. 8913-8921, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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