Development of a transgenic mouse model susceptible to human coronavirus 229E
- Caroline Lassnig*,
- Carlos M. Sanchez†,
- Monika Egerbacher‡,
- Ingrid Walter‡,
- Susanne Majer*,
- Thomas Kolbe§,
- Pilar Pallares¶,
- Luis Enjuanes†,∥, and
- Mathias Müller§,**,††
- *Ludwig Boltzmann Institute for Immunogenetic, Cytogenetic, and Molecular Genetic Research, 1210 Vienna, Austria; †Department of Molecular and Cell Biology and ¶Animal Facility, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Científicas, 28049 Madrid, Spain; Institutes of ‡Histology and Embryology and **Animal Breeding and Genetics, University of Veterinary Medicine, 1210 Vienna, Austria; and §Department of Agrobiotechnology, IFA-Tulln, Institute of Biotechnology in Animal Production, University of Natural Resources and Applied Life Sciences, 3430 Tulln, Austria
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Edited by Bernard Moss, National Institutes of Health, Bethesda, MD (received for review November 18, 2004)
Abstract
Human coronavirus (HCoV) 229E is a group 1 coronavirus and is specific to humans. So far, no animal model is available to study the pathogenesis of infection by HCoV-229E. We show here that the expression of aminopeptidase N (APN, also termed CD13), the receptor for HCoV-229E, is required but not sufficient to confer susceptibility in vivo. HCoV-229E infection was facilitated by crossing APN transgenic mice into signal transducers and activators of transcription (Stat) 1 null mice and by adaptation of HCoV-229E to grow in primary APN transgenic, Stat1 null fibroblasts. Double transgenic mice allow the study of human coronavirus group 1 infections in an animal model, in particular, viral tropism, replication, recombination, and spread in an immunocompromised situation. Furthermore, these mice provide an important tool for the evaluation of biosafety and efficacy of coronavirus-based vectors.
Footnotes
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↵ ∥To whom correspondence may be addressed at: Department of Molecular and Cell Biology, Centro Nacional de Biotecnologia, Campus University Autonoma, Cantoblanco, 28049 Madrid, Spain. E-mail: l.enjuanes{at}cnb.uam.es. ††To whom correspondence may be addressed at: Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Veterinärplatz 1, 1210 Vienna, Austria. E-mail: mathias.mueller{at}vu-wien.ac.at.
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Author contributions: L.E. and M.M. designed research; C.L., C.M.S., S.M., T.K., and P.P. performed research; C.L., C.M.S., and T.K. contributed new reagents/analytic tools; C.L., M.E., and I.W. analyzed data; and C.L., L.E., and M.M. wrote the paper.
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This paper was submitted directly (Track II) to the PNAS office.
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Abbreviations: HCoV, human coronavirus; APN, aminopeptidase N; hAPN, human APN; S, coronavirus spike; PEF, primary embryonic fibroblast; Stat, signal transducers and activators of transcription.
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See Commentary on page 8073.
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Freely available online through the PNAS open access option.
- Copyright © 2005, The National Academy of Sciences
