Re-purposing Plant Viruses to Protect Agricultural Crops from Parasitic Pests

As of 2017, the human population has reached a striking number of ~7.5 billion. Consequently, one of the major challenges we face in the upcoming years is to increase food production as well as to ensure food safety and security to feed the growing world population. In particular, it is becoming more important to maximize crop yields through the use of next-generation pest control. Toward this goal, Biomedical Engineering PhD student Paul Chariou and Professor Nicole Steinmetz at Case Western Reserve University have developed an agricultural drug delivery nanotechnology to treat crops infected by microscopic roundworms called nematodes.

 

Many kinds of nematodes reside in soil, including beneficial predator nematodes that can parasitize insects, bacteria, or fungi, and help with the decomposition of organic matter to form compost. On the other hand, other nematodes are a major concern to farmers and garden lovers; these pests can infect agricultural crops as well as farm animals. Among them, plant parasitic nematodes such as the root-knot Meloidogyne spp can infect more than 3,000 plant species including corn, potatoes, tomatoes, lettuce, and various fruit trees. These “invisible enemies” use their needle-like mouth to enter and parasitize the roots of crops, preventing the circulation of water and nutrients to the rest of the plant. In addition, nematodes promote crack formation on the surface of roots, which leaves plants vulnerable to infections by bacteria and fungi. Overall, plant parasitic nematodes cumulate to an astonishing $157 billion annual loss in crop production and treatment cost across the globe.

 

Farmers have employed crop rotation as a means to control nematode infestation with little to no success due to the vast range of host species. Alternatively, genetically modified crops resistant to nematodes are being developed, but they are expensive and take years to engineer. As of today, the most economically viable treatment option remains the use of pesticides against nematodes, called nematicides, which come with their own set of challenges. In order to eradicate the pest, nematicides must 1) reach the root level of crops where nematodes reside, 2) persist over prolonged time periods, and 3) accumulate in quantities large enough to effectively kill the nematodes. Unfortunately, nematicide molecules have difficulty to transport deep within the soil. Nematicides ‘stick’ to the soil particles and therefore do not reach their target but accumulate close to the surface of crops. In fact, 90% of pesticides applied in the field will never reach their target pest and are lost or degraded in the environment. As a consequence, extended persistence of nematicide in the field increases the risk of crop, soil, and groundwater chemical contamination, and ultimately increases the risk of human exposure to these toxins. 

 

To attack the problem at its roots, Chariou and Steinmetz turned toward a nanotechnology approach to formulate the next-generation of nematicides. Nanotechnologies have emerged in the last two decades to deliver pesticides in a controlled and targeted manner. Compared to free pesticides, nanoscale materials used as pesticide carriers can travel deeper in soil to effectively eradicate the desired pest. The encapsulation of pesticides in nanomaterials also protects farmers from being exposed to these toxins and prevents their immature degradation in soil. While several groups have investigated the use of synthetic nanocarriers, these polymer or phospholipid materials may contaminate and accumulate in the environment for long periods of time. Chariou and Steinmetz’s twist to nanotechnology is the application of nanoparticles derived from plant viruses.

 

It may seem counterintuitive to re-purpose a plant virus as a therapeutic. However, when looking at a plant virus from a materials science and nanotechnology perspective, these materials offer several advantages over their synthetic counterparts. From a manufacturing perspective, plant viral nanoparticles can be produced in large quantities (500 milligrams of virus for 100 grams of leaves) within a few days to a few weeks, and at a low price ($2 for 100 milligrams of virus). Unlike synthetic nanoparticles, viral nanoparticles are produced using cheap media (soil and seeds) and do not require the use of expensive growth media or potentially toxic solvents. From a human health perspective, the virus is incapable of infecting the human host, thus offering an added layer of safety. From an environmental perspective, plant viruses are ubiquitous; many plant viruses are soil borne. While some viruses cause plant disease, others have narrow host ranges and do not harm crops. In fact, a plant virus-based product is already used in field; SolviNix LC is an herbicide produced by BioProdex; the active ingredient is the plant virus Tobacco mild green virus (TMGMV). The product is approved by the American Environmental Protection Agency (EPA) in the state of Florida for the treatment of the invasive tropical soda apple weed. 

 

Building on this, the Steinmetz Lab turned toward the development of TMGMV as a nanotechnology platform to transport nematicides to the roots of plants infected by nematodes. TMGMV is a soil-borne plant virus with properties that are hypothesized to confer enhanced soil mobility. The idea pursued is to use the TMGMV particle as a carrier of the nematicide to enhance stability and transport through soil, therefore enabling more efficacious treatment of nematode infested crops while reducing the pesticide dose applied in the field. The ultimate goal is to protect the environment and the general public from the toxic nature of pesticides. 

 

The TMGMV particle forms a hollow nanotube structure, like a paper towel roll, but 1,000,000 times smaller. More precisely, TMGMV forms a hollow nanotube with dimension of 300x18 nm and a central channel of 4 nm. Chariou and Steinmetz showed that nematicides could be loaded into this central channel, thus re-purposing TMGMV as a carrier. TMGMV can carry up to 1,500 drugs per particle. The TMGMV-nematicide formulation maintained efficacy and effectively immobilized and killed nematodes in liquid cultures. Most importantly, the TMGMV-nematicide formulation exhibited much greater soil mobility compared to free nematicide, which would allow the pesticide to reach nematodes that reside at the root level. 

 

 

This work was published at the top-tier nanotechnology journal, ACS Nano (Chariou P.L., Steinmetz N.F. (2017) Delivery of Pesticides to Plant Parasitic Nematodes Using Tobacco Mild Green Mosaic Virus as a Nanocarrier. ACS Nano 11, 4719-4730). In ongoing studies, the team is further investigating the soil transport behavior of TMGMV loaded with various commercial nematicides compared to free nematicides. These complex studies should highlight which dose regimen should be applied on crop fields based on the texture of the soil, its composition (clay, sand, and silt), the acidity of the soil, as well as the root depth. The team is eager to translate this next-generation crop treatment technology from the research lab to in field applications.

 

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