Tuesday, January 21, 2014

GMOs resistant to viruses. How does that work?

During a nerdy web-surfing episode, I stumbled upon a database that listed commercial GMOs, the regions where they've been approved, and a description of the genetic modification. Pretty handy. While scrolling through the list, I observed that one of the more common modifications is to confer viral resistance or immunity to the plant. The transgene that is added to the plant is a protein from the virus itself. And then I wondered, "how does that work? How does a protein from the virus give the plant immunity?" I knew that plants didn't have antibodies, but that was about it. During my bachelor's degree, I took quite a few plant courses ("Plants as Human Resources" was really popular), including plant biochem courses in later years to meet the requirements for my biochemistry major. But thinking back on everything I learned, I don't think that the topic of the plant immune system ever came up.

As usual, the interwebs didn't let me down. I found a very confusing 2006 review in Nature entitled "The plant immune system". Plants don't have "mobile defender cells". Despite the fact that Google will try to convince you that these are accessories for your cell phones, the role of these defender cells (which include our white blood cells) is to swoop in and "zap" foreign cells. Instead of this highly effective mobile defense system, plants have an "innate immune system" where proteins on the surface of cells and within them recognize signals from pathogens and microbes. One study found that the Arabidopsis plant turns on over 1100 genes in less than 1 hour when it recognizes bacterial pathogens. Successful pathogens either manage to suppress the plant's immune response or dodge it altogether.

The next paper I read was a fantastic review written in 1999 by one of the scientists who made the first transgenic plant with a virus protein. Before I continue, the spouse-like voice in my head is telling me that I'll need to explain the structure of a virus.

File:TMV structure simple.png
From Wikimedia Commons
Viruses are weird because it's hard to classify them as "living". They need a host cell so that they can replicate and spread, which is why they infect other organisms. They have several components and I'll focus on two of these in this article: the genetic material which is generally RNA, and a protein coat that protects the genetic material. In order to replicate and spread, the virus uses the host cell's machinery to make more of its protein components. Pretty sneaky, eh? Sort of like a thief breaking their way into your house and taking advantage of your lovely plumbing by taking a dump in your bathroom, on top of stealing all your stuff. That last analogy was inspired by my kid, who is currently pointing at his diaper and saying "Poop". I wonder what he needs?

Getting back to plant viruses. And yes... I did change his diaper.

So the review outlines that the first proposal to create a transgenic plant with a virus coat protein was made in 1981, when the author suggested creating plants resistant to the tobacco mosaic virus. The tobacco mosaic virus was the first virus ever discovered, is one of the most thoroughly studied viruses, and infects species other than tobacco (including tomatoes). The study was a joint collaboration between Monsanto and WashU in St Louis. It took several years until a tobacco plant was successfully made that was resistant to the virus, and where the next generation of plants were also resistant to infection by the virus.  Some plants were not resistant altogether, but it took longer for these plants to develop symptoms when compared to controls. The data were published in the journal Science in 1986 and the process was dubbed "coat-protein-mediated resistance" or CP-MR.

To understand how CP-MR works, several experiments were conducted. In the first, they infected the tobacco plants with the genetic material from the virus, meaning that the virus was missing the protective protein coat. They found that the genetically modified plants were more susceptible to infection by the genetic material when compared to control plants. That suggested that there was something in the coat-protein that had been added to the plant that interfered with the infection process early on. As an analogy, think of the virus as the pulp of an orange, as infection as the mess you leave on your counter when you squeeze out the juice, and the protein coat as the rind. In order to squirt the orange juice all over your kitchen counter, you have to remove the rind or at least cut through it. If there's something preventing you from cutting open the orange or removing the rind, then you'll never make a mess on your counter (i.e. infection will never happen). In this experiment, they handed over a pre-peeled orange for your squeezing pleasure, and found that a mess was easily made. So the results suggest that CP-MR doesn't have to do with the "squeezing" or infection process, rather, something prevents the removal of the rind. In the late 80's, several different studies were performed whose results backed up the hypothesis that the coat-protein transgene interferes with viral disassembly.

A few other interesting studies have been performed over the years, in attempts to better understand CP-MR. Some pretty cool experiments were the infection of the transgenic plants with different viruses that were similar to the tobacco virus, but not identical. They found that it's important for the coat proteins on the virus be similar to the coat protein genes in the transgenic plant, but that the sequence of the RNA in the virus doesn't really matter. In thinking about this, I thought it was an important finding because it would imply that the virus could mutate, but that CP-MR would continue working, although it may be to a lesser extent.

So, I like this whole story about CP-MR for many reasons. I think it's a cool, quirky oddity from nature. But I also think that it's a nice success story for the joint funding of research by public and private funds. Of course, the patent for CP-MR belongs to Monsanto and WashU, but apparently they've been working with different global institutions to create disease resistant crops. I have no doubt that Monsanto is making kajillions of dollars off of this, but it has led to the understanding of plant viruses, as well as the creation of some important crops. Some crops that use CP-MR are squash, papaya, and potato, and there are a few others approved in different countries.

Feel free to suggest future topics below.

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