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Journal of Virology, August 2004, p. 8824-8834, Vol. 78, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.16.8824-8834.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Human Respiratory Coronavirus OC43: Genetic Stability and Neuroinvasion

Julien R. St-Jean,¹ Hélène Jacomy,¹ Marc Desforges,¹ Astrid Vabret,² François Freymuth,² and Pierre J. Talbot^1*

Laboratory of Neuroimmunovirology, INRS-Institut Armand-Frappier, Laval, H7V 1B7 Quebec, Canada,¹ Laboratoire de Virologie Humaine et Moléculaire, Centre Hospitalier Régional et Universitaire de Caen, 14033 Caen, France²

Received 28 January 2004/ Accepted 7 April 2004

The complete genome sequences of the human coronavirus OC43 (HCoV-OC43) laboratory strain from the American Type Culture Collection (ATCC), and a HCoV-OC43 clinical isolate, designated Paris, were obtained. Both genomes are 30,713 nucleotides long, excluding the poly(A) tail, and only differ by 6 nucleotides. These six mutations are scattered throughout the genome and give rise to only two amino acid substitutions: one in the spike protein gene (I958F) and the other in the nucleocapsid protein gene (V81A). Furthermore, the two variants were shown to reach the central nervous system (CNS) after intranasal inoculation in BALB/c mice, demonstrating neuroinvasive properties. Even though the ATCC strain could penetrate the CNS more effectively than the Paris 2001 isolate, these results suggest that intrinsic neuroinvasive properties already existed for the HCoV-OC43 ATCC human respiratory isolate from the 1960s before it was propagated in newborn mouse brains. It also demonstrates that the molecular structure of HCoV-OC43 is very stable in the environment (the two variants were isolated ca. 40 years apart) despite virus shedding and chances of persistence in the host. The genomes of the two HCoV-OC43 variants display 71, 53.1, and 51.2% identity with those of mouse hepatitis virus A59, severe acute respiratory syndrome human coronavirus Tor2 strain (SARS-HCoV Tor2), and human coronavirus 229E (HCoV-229E), respectively. HCoV-OC43 also possesses well-conserved motifs with regard to the genome sequence of the SARS-HCoV Tor2, especially in open reading frame 1b. These results suggest that HCoV-OC43 and SARS-HCoV may share several important functional properties and that HCoV-OC43 may be used as a model to study the biology of SARS-HCoV without the need for level three biological facilities.

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* Corresponding author. Mailing address: Laboratory of Neuroimmunovirology, INRS-Institut Armand-Frappier, 531 Boulevard des Prairies, Laval, H7V 1B7 Quebec, Canada. Phone: (450) 686-5515. Fax: (450) 686-5566. E-mail: pierre.talbot{at}inrs-iaf.uquebec.ca.

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Journal of Virology, August 2004, p. 8824-8834, Vol. 78, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.16.8824-8834.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• St-Jean, J. R., Desforges, M., Almazan, F., Jacomy, H., Enjuanes, L., Talbot, P. J. (2006). Recovery of a Neurovirulent Human Coronavirus OC43 from an Infectious cDNA Clone.. J. Virol. 80: 3670-3674 [Abstract] [Full Text]  
• Vijgen, L., Lemey, P., Keyaerts, E., Van Ranst, M., St-Jean, J. R., Jacomy, H., Desforges, M., Talbot, P. J., Vabret, A., Freymuth, F. (2005). Genetic Variability of Human Respiratory Coronavirus OC43. J. Virol. 79: 3223-3225 [Full Text]