Many viruses accumulate to high titers in their natural hosts; plant viruses, for example, can be isolated in gram scales from a kilogram of infected leaf material. Infection of plants can be achieved by mechanical inoculation using either homogenized plant tissue from infected leaves, or purified viral nanoparticles (VNPs). Transcription and expression of the viral ribonucleic acid lead to the production of chimeric capsid proteins, which assemble into chimeric VNPs and spread systemically. Heterologous expression systems are of critical importance for large-scale production of virus-like particles (VLPs) and mutant particles. Heterologous expression systems used to generate VLPs include use of bacteria, yeast, insect cells, and mammalian cells. Escherichia coli is one of the most widely used hosts for production of heterologous proteins in general. The advantages of heterologous protein expression in plants are high yields, ease of purification, lack of mammalian contaminants, ease of manipulation, eukaryotic modification machinery, ease of scale-up, and cost-effectiveness.