Braconid wasp from Forestry Images.

In Polydnaviruses: Nature’s GMOs, I wrote about how wasps use viruses to disable the immune defenses of their hosts. Braconid and ichneumonid wasps use a system that genetically modifies their hosts in order to shut their immune systems down.

So how does this all work?

A good system to use to describe how polydnavirus proteins work is the ankyrin/vankyrin pathways. It’s easy to visualize how they function and many other functions (Toll, Phenoloxidase silencing, etc) work in an indentical manner.

Apoptosis is a vital immune defense where the cell begins producing enzymes called capsases which indiscriminately chew proteins up in the cell.  If there’s a virus infecting the cell, the simplest way to save the whole organism is to destroy the infected cell. Destroy the infected cell, ensure no viral replication takes place, save the whole critter. Lots viruses have antiapoptotic proteins, and polydnaviruses use similar proteins to stop other immune processes which would kill the parasitoid larvae.

In the simplest apoptosis pathway, we start with NFkB proteins floating around the cytoplasm of the cell bound to an IkB protein in a fashion that’s not unlike a zipper. What would be comparable to the ‘teeth’ of the zipper is a specific structure called an ankyrin domain which links the proteins together.

There are two proteins linked together in the picture below. The one on the right is a protein which binds to a regulatory portion of a gene and tells RNA polymerase to transcribe a certain gene…in this example, capsase. The other protein, the IkB (Inhibitor kB protein) prevents this protein from going into the nucleus and triggering the capsases.

In normal circumstances, this only happens when a receptor binds to some sort of negative signal which signals bad news for the cell. In an actual system, this could be viral or bacterial proteins. Maybe even a burst of ultraviolet light. In this example, I’ve used a picture of actor Gary Busey as an example of an immune challenge.

After the ‘bad’ signal binds to the receptor, a cascade of events commences within the cell. The IkB protein dissociates from the cell and gets broken down. The NFkB protein then travels to the nucleus where it induces the production of capsases which results in the destruction of proteins within the cells.

The polydnavirus proteins encode a hacked version of the IkB proteins. They’re the same as the proteins encoded in the wasp, except they’re missing the part of the protein which responds to the signals sent by the receptor. This results in an IkB protein which doesn’t disassociate from the NFkB when the apoptosis signal goes out. If the IkB and NFkB proteins don’t disassociate, the NFkB proteins can’t induce apoptosis.

If you look at the pictures above, you can pretty easily tell which cell culture is expressing the vankyrin (viral ankyrin) proteins. The cells were exposed to a burst of ultraviolet light, and the cells on the right were expressing the protein which inhibits apoptosis.

Gene duplication with modification is a common theme in polydnavirus systems. Another of my favorite proteins, the Cotesia plutellae Bracovirus H4 actually works through epigenetics. H4 is a histone protein which changes the structure of DNA and regulates gene expression when acetyl groups are added to the amino acids at the end of the protein. A bracovirus symbiotic with Cotesia plutellae (CpBV) encodes a version of this histone protein which is essentially the same as that of it’s host with the exception of the amino acids at the end of the protein. These modified histone proteins have an effect on another part of the immune system, the blood cells which surround invaders and encapsulate them. These ‘blood cells’ are also known as hemocytes. The CpBV H4 protein severely reduces hemocyte spreading, and eliminates this threat to the wasp.

In short, in polydnaviral proteins, there is a very common theme which emerges. Many of them exist in the wasp genome and have been slightly modified so that they can’t be activated at the correct time, thereby interfering with vital cell processes.

Fath-Goodin A, Kroemer JA, & Webb BA (2009). The Campoletis sonorensis ichnovirus vankyrin protein P-vank-1 inhibits apoptosis in insect Sf9 cells. Insect molecular biology, 18 (4), 497-506 PMID: 19453763

Gad W, & Kim Y (2008). A viral histone H4 encoded by Cotesia plutellae bracovirus inhibits haemocyte-spreading behaviour of the diamondback moth, Plutella xylostella. The Journal of general virology, 89 (Pt 4), 931-8 PMID: 18343834

Thoetkiattikul H, Beck MH, & Strand MR (2005). Inhibitor kappaB-like proteins from a polydnavirus inhibit NF-kappaB activation and suppress the insect immune response. Proceedings of the National Academy of Sciences of the United States of America, 102 (32), 11426-31 PMID: 16061795

So what makes Braconid (and Ichneumonid!) wasps so strange, and why am I writing about them on Biofortified?

Well, it turns out that Braconid and Ichneumonid wasps actually modify their hosts genetically by doing something which very much resembles gene therapy.

Most of the time we modify organisms because we want them to do something they currently don’t do. To use the example of BT corn, the corn plant was a better host for the European corn borer than we liked, so we took a protein from a bacteria which was known to kill the larvae which bored into the stalks but also known to be harmless to mammals and made the corn produce the protein which harmed the caterpillar and thus made a relatively bug-proof crop as far as the major pest was concerned.

Well, the caterpillars also produce genes which are bad for the wasps…these genes are involved in the immune system. The immune system’s role is to kill foreign invaders and if you fall under that category, you’re going to need a way to flout the immune system. The wasps in the video above accomplish this through a very strange symbiosis: they inject viral particles into the caterpillar to knock it’s immune system out.

These viruses are very strange because they contain very few viral genes. Many of the genes they contain are actually very similar to the immune system of the wasp. They don’t replicate, but they travel to certain points of the fat body and nervous system and begin producing proteins which have a great many functions, from increasing the amount of food the caterpillar consumes to producing proteins which interfere with immune functions.

It may seem odd to some that a blog that mostly focuses on controversies in modern agriculture would ask someone who studies insects to write on their site, but it’s not as counter intuitive as you think. Insects are a huge part of agriculture because they are our biggest competitors for food. One of the most common types of genetically modified corn, the various BT cultivars, were developed to fight the European Corn Borer, Ostrinia nubilalis, which is a tiny Crambid moth which burrows into the stalks of the plants and eventually kills them.

An entomologist writing for a site which explores the politics of Genetically Modified Organisms makes sense for another reason, and that’s because entomologists sometimes modify the genes of insects in order to do their work. Some of this occurs naturally, through the actions of polydnavirus particles some parasitoid wasps inject into their hosts to control the behavior, development, and immune reactions of that host. Sometimes it’s simple and artificial such as releasing insects sterilized with X-ray radiation in order to fight diseases and crop pests. Some of the things that entomologists work with aren’t necessarily insects but are used to control their populations. A great example of this is the modification of viruses as systems which are used to deliver pesticides directly to the insects rather than spraying the environment with pesticides.

What I hope to do is to use this site to educate the public about some of the GMOs you may hear about on the news, and I hope to make people realize that these are wonderful inventions that better humanity. New things are definitely a little scary at first, but education is the best way to overcome these fears.

Since this is my first post, let’s explore some really basic insect biology that might be necessary to understand parts of my posts. Insects go through two types of development: hemimetabolous, or incomplete metamorphosis and holometabolous which is commonly known as complete metamorphosis.

Here’s an example of hemimetabolous or incomplete development. The video below depicts the life cycle of a cicada which begins as an egg and then develops through a series of nymphal stages before maturing into an adult. Notice how the adults are very similar to the nymphs with the obvious exception of wings. Also notice how they have a relatively similar ecological role, both feed on sap but in slightly different areas.

This is an example of holometabolous development. The butterfly in the video has a very strange parasitic relationship with ants. This butterfly goes through four stages: egg, larva, pupa and adult. Notice how the larva looks nothing like the adult, and how the larva has a completely different role than the adult. In this case, the adult feeds on nectar from flowers while the larva is a parasite in the ant nest.