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Journal of Virology, September 2004, p. 9073-9083, Vol. 78, No. 17
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.17.9073-9083.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The N-Terminal Region of the Murine Coronavirus Spike Glycoprotein Is Associated with the Extended Host Range of Viruses from Persistently Infected Murine Cells

Jeanne H. Schickli,1,{dagger} Larissa B. Thackray,1,{ddagger} Stanley G. Sawicki,2 and Kathryn V. Holmes1*

Department of Microbiology, University of Colorado Health Sciences Center, Denver, Colorado,1 Department of Microbiology and Immunology, Medical College of Ohio, Toledo, Ohio2

Received 10 December 2003/ Accepted 23 April 2004

Although murine coronaviruses naturally infect only mice, several virus variants derived from persistently infected murine cell cultures have an extended host range. The mouse hepatitis virus (MHV) variant MHV/BHK can infect hamster, rat, cat, dog, monkey, and human cell lines but not the swine testis (ST) porcine cell line (J. H. Schickli, B. D. Zelus, D. E. Wentworth, S. G. Sawicki, and K. V. Holmes, J. Virol. 71:9499-9507, 1997). The spike (S) gene of MHV/BHK had 63 point mutations and a 21-bp insert that encoded 56 amino acid substitutions and a 7-amino-acid insert compared to the parental MHV strain A59. Recombinant viruses between MHV-A59 and MHV/BHK were selected in hamster cells. All of the recombinants retained 21 amino acid substitutions and a 7-amino-acid insert found in the N-terminal region of S of MHV/BHK, suggesting that these residues were responsible for the extended host range of MHV/BHK. Flow cytometry showed that MHV-A59 bound only to cells that expressed the murine glycoprotein receptor CEACAM1a. In contrast, MHV/BHK and a recombinant virus, k6c, with the 21 amino acid substitutions and 7-amino-acid insert in S bound to hamster (BHK) and ST cells as well as murine cells. Thus, 21 amino acid substitutions and a 7-amino-acid insert in the N-terminal region of the S glycoprotein of MHV/BHK confer the ability to bind and in some cases infect cells of nonmurine species.

* Corresponding author. Mailing address: Dept of Microbiology, Campus Box B-175, UCHSC, 4200 East 9th Ave., Denver, CO 80262. Phone: (303) 315-7329. Fax: (303) 315-6785. E-mail: kathryn.holmes{at}uchsc.edu.

{dagger} Present address: Medimmune Vaccines, Mountain View, Calif.

{ddagger} Present address: Washington University, St. Louis, Mo.

Journal of Virology, September 2004, p. 9073-9083, Vol. 78, No. 17
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.17.9073-9083.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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