title: Systemic trafficking of plant virus nanoparticles in mice via the oral route.
abstract: 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.
authors.affiliation: Center for Integrative Molecular Biosciences (CIMBio), The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
authors.forename: Chris S
authors.initials: CS
authors.lastname: Rae
authors.forename: Ing Wei
authors.initials: IW
authors.lastname: Khor
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Destito
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Gonzalez
authors.forename: Pratik
authors.initials: P
authors.lastname: Singh
authors.forename: Diane M
authors.initials: DM
authors.lastname: Thomas
authors.forename: Mayra N
authors.initials: MN
authors.lastname: Estrada
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Powell
authors.forename: M G
authors.initials: MG
authors.lastname: Finn
authors.forename: Marianne
authors.initials: M
authors.lastname: Manchester
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002264:Carboxylic Acids; D017798:Comovirus / Q000472:pathogenicity / Q000648:ultrastructure*; D007887:Fabaceae / Q000821:virology; D005260:Female; D005456:Fluorescent Dyes; D005750:Gastric Juice / Q000821:virology; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000648:ultrastructure*; D036103:Nanotechnology; D014018:Tissue Distribution
chemical_list: D002264:Carboxylic Acids; D005456:Fluorescent Dyes; C436864:Oregon Green 488 carboxylic acid