The plant virus, cowpea mosaic virus (CPMV), is increasingly being used as a nanoparticle platform for multivalent display of peptides. A growing variety of applications have employed the CPMV display technology including vaccines, antiviral therapeutics, nanoblock chemistry, and materials science. CPMV chimeras can be inexpensively produced from experimentally infected cowpea plants and are completely stable at 37 degrees C and low pH, suggesting that they could be used as edible or mucosally-delivered vaccines or therapeutics. However, the fate of CPMV particles in vivo, or following delivery via the oral route, is unknown. To address this question, we examined CPMV in vitro and in vivo. CPMV was shown to be stable under simulated gastric conditions in vitro. The pattern of localization of CPMV particles to mouse tissues following oral or intravenous dosing was then determined. For several days following oral or intravenous inoculation, CPMV was found in a wide variety of tissues throughout the body, including the spleen, kidney, liver, lung, stomach, small intestine, lymph nodes, brain, and bone marrow. CPMV particles were detected after cardiac perfusion, suggesting that the particles entered the tissues. This pattern was confirmed using methods to specifically detect the viral capsid proteins and the internal viral RNA. The stability of CPMV virions in the gastrointestinal tract followed by their systemic dissemination supports their use as orally bioavailable nanoparticles.

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.Global control of infectious diseases is dependent upon the development of novel, inexpensive and easily produced vaccine and antiviral reagents. In regions where infections are endemic, the use of appropriate antimicrobial reagents is largely limited by cost and the lack of equipment and facilities for appropriate delivery of the reagents. The use of plant viruses such as the cowpea mosaic virus (CPMV) as biomolecular platforms for designing antiviral agents and vaccines overcomes many of these obstacles. CPMV provides the advantages of inexpensive production of large quantities of material, with up to 1 to 2 g of virus produced per kilogram of infected cowpea plants. In addition, plant virus particles are generally stable to extremes of temperature and pH; for example, CPMV can withstand temperatures up to 60°C and pH levels as low as 1.0 to 2.0 (18), and this stability is an advantage for use in tropical and/or rural areas, where continuous refrigeration is not readily available. Finally, the lack of contaminating animal cells and viruses in plant reagent preparations is beneficial.The CPMV chimera technology for presenting heterologous peptides is based on the crystal structure of the virus capsid (3, 9). The CPMV capsid consists of 60 copies each of a large (L) and small (S) protein that are arranged with icosahedral symmetry. One L protein consisting of two jelly roll ␤-barrels and one S protein consisting of a single jelly roll ␤-barrel make up the asymmetric unit of the capsid. There are three copies of the L protein arranged around each threefold axis of symmetry, and five copies of the S protein are arranged around each fivefold axis of symmetry. In the S protein, surface-exposed loops that do not appear to be involved in intersubunit contact exhibit high variability among different members of the comovirus family of plant viruses, of which CPMV i...