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