Soluble receptor-mediated targeting of mouse hepatitis coronavirus to the human epidermal growth factor receptor

T Würdinger, M H Verheije, K Broen, B J Bosch, B J Haijema, C A M de Haan, V W van Beusechem, P J M Rottier, W.R. Gerritsen

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Abstract

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.

Original languageEnglish
Pages (from-to)15314-15322
Number of pages9
JournalJournal of Virology
Volume79
Issue number24
DOIs
Publication statusPublished - Dec 2005

Cite this

Würdinger, T., Verheije, M. H., Broen, K., Bosch, B. J., Haijema, B. J., de Haan, C. A. M., ... Gerritsen, W. R. (2005). Soluble receptor-mediated targeting of mouse hepatitis coronavirus to the human epidermal growth factor receptor. Journal of Virology, 79(24), 15314-15322. https://doi.org/10.1128/JVI.79.24.15314-15322.2005