Novel strategy for inhibiting viral entry by use of a cellular receptor-plant virus chimera

Journal of Virology
Ing Wei KhorMarianne Manchester

Abstract

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.

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Citations

Nov 20, 2003·Trends in Biotechnology·Adam Zlotnick, Stephen J Stray
Jan 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jingchuan SunBogdan Dragnea
Apr 30, 2013·Journal of the American Chemical Society·Yen-Ting LaiTodd O Yeates
Sep 10, 2015·Vaccines·Marie-Ève LebelAlain Lamarre
Sep 28, 2005·Virology·Chris S RaeMarianne Manchester
Sep 25, 2012·Molecular Pharmaceutics·Clorissa L Washington-HughesQian Wang
Jul 23, 2004·Antiviral Chemistry & Chemotherapy·Dale L Barnard
Apr 24, 2003·Medicinal Research Reviews·Raffaele SaladinoAnna Teresa Palamara
Jul 3, 2009·Small·Aihui MahamYuehe Lin
Oct 21, 2013·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Leah P ShriverMarianne Manchester
Apr 13, 2006·Nano Letters·Chao ChenBogdan Dragnea
Jun 5, 2007·Journal of the American Chemical Society·Hannah N BarnhillQian Wang

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