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Journal of Virology, May 2002, p. 4412-4419, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4412-4419.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Novel Strategy for Inhibiting Viral Entry by Use of a Cellular Receptor-Plant Virus Chimera{dagger}

Ing Wei Khor,1 Tianwei Lin,2 Johannes P. M. Langedijk,2,{ddagger} John E. Johnson,2 and Marianne Manchester1*

Department of Cell Biology, Center for Integrative Molecular Biosciences,1 Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 920372

Received 4 October 2001/ Accepted 22 January 2002

The plant virus cowpea mosaic virus (CPMV) has recently been developed as a biomolecular platform to display heterologous peptide sequences. Such CPMV-peptide chimeras can be easily and inexpensively produced in large quantities from experimentally infected plants. This study utilized the CPMV chimera platform to create an antiviral against measles virus (MV) by displaying a peptide known to inhibit MV infection. This peptide sequence corresponds to a portion of the MV binding site on the human MV receptor CD46. The CPMV-CD46 chimera efficiently inhibited MV infection of HeLa cells in vitro, while wild-type CPMV did not. Furthermore, CPMV-CD46 protected mice from mortality induced by an intracranial challenge with MV. Our results indicate that the inhibitory CD46 peptide expressed on the surface of CPMV retains virus-binding activity and is capable of inhibiting viral entry both in vitro and in vivo. The CD46 peptide presented in the context of CPMV is also up to 100-fold more effective than the soluble CD46 peptide at inhibiting MV infection in vitro. To our knowledge, this study represents the first utilization of a plant virus chimera as an antiviral agent.


* Corresponding author. Mailing address: Department of Cell Biology, CB-248, Center for Integrative Molecular Biosciences, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-8086. Fax: (858) 784-2139. E-mail: marim{at}scripps.edu.

{dagger} This is manuscript 14460-NP from The Scripps Research Institute.

{ddagger} Present address: Department of Mammalian Virology, Institute of Animal Science and Health (ID-DLO), 8200AB Lelystad, The Netherlands.


Journal of Virology, May 2002, p. 4412-4419, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4412-4419.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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