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Journal of Virology, December 2005, p. 15314-15322, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15314-15322.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Soluble Receptor-Mediated Targeting of Mouse Hepatitis Coronavirus to the Human Epidermal Growth Factor Receptor

T. Würdinger,1,2,{dagger} M. H. Verheije,1,2,{dagger} K. Broen,1 B. J. Bosch,1 B. J. Haijema,1 C. A. M. de Haan,1 V. W. van Beusechem,2 W. R. Gerritsen,2 and P. J. M. Rottier1*

Virology Division, Department of Infectious Diseases & Immunology, Utrecht University, 3584 CL Utrecht,1 Division of Gene Therapy, Department of Medical Oncology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands2

Received 5 August 2005/ Accepted 27 September 2005

The mouse hepatitis coronavirus (MHV) infects murine cells by binding of its spike (S) protein to murine CEACAM1a. The N-terminal part of this cellular receptor (soR) is sufficient for S binding and for subsequent induction of the conformational changes required for virus-cell membrane fusion. Here we analyzed whether these characteristics can be used to redirect MHV to human cancer cells. To this end, the soR domain was coupled to single-chain monoclonal antibody 425, which is directed against the human epidermal growth factor receptor (EGFR), resulting in a bispecific adapter protein (soR-425). The soR and soR-425 proteins, both produced with the vaccinia virus system, were able to neutralize MHV infection of murine LR7 cells. However, only soR-425 was able to target MHV to human EGFR-expressing cancer cells. Interestingly, the targeted infections induced syncytium formation. Furthermore, the soR-425-mediated infections were blocked by heptad repeat-mimicking peptides, indicating that virus entry requires the regular S protein fusion process. We conclude that the specific spike-binding property of the CEACAM1a N-terminal fragment can be exploited to direct the virus to selected cells by linking it to a moiety able to bind a receptor on those cells. This approach might be useful in the development of tumor-targeted coronaviruses.

* Corresponding author. Mailing address: Virology Division, Department of Infectious Diseases & Immunology, Utrecht University, 3584 CL Utrecht, The Netherlands. Phone: 31 30 253 2485. Fax: 31 30 253 6723. E-mail: p.rottier{at}vet.uu.nl.

{dagger} T.W. and M.H.V. contributed equally to this work.

Journal of Virology, December 2005, p. 15314-15322, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15314-15322.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Verheije, M. H., Lamfers, M. L. M., Wurdinger, T., Grinwis, G. C. M., Gerritsen, W. R., van Beusechem, V. W., Rottier, P. J. M. (2009). Coronavirus Genetically Redirected to the Epidermal Growth Factor Receptor Exhibits Effective Antitumor Activity against a Malignant Glioblastoma. J. Virol. 83: 7507-7516 [Abstract] [Full Text]  
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