Braconid parasite wasps have practiced gene therapy for a hundred million years

Feb 17 2009

Braconid parasite wasps and their caterpillar hosts form a unique host-parasite model: the wasps lay their eggs inside the caterpillars and simultaneously inject some viral particles to get around the host's defenses and control its physiology.

The genes from these viral particles have now been identified in the wasp's own genome by a team at the Institut de recherche sur la biologie de l'insecte (CNRS/Université François-Rabelais Tours), in collaboration with a laboratory at University of Berne and Genoscope d'Evry. These genes came from a virus captured by a common ancestor of these wasps 100 million years ago. These results, published in Science 13 February 2009, could provide new means of designing transfer vectors for gene therapy.

Wasps of the family Braconidae reproduce by laying their eggs in caterpillars, which then serve as food for the developing wasp larvae. However, the body of a caterpillar is a hostile environment, with an efficient defense system that forms a capsule of immune cells around foreign objects. To get around these defenses, when the wasp lays her eggs in the caterpillar, she also injects some special particles made in her ovaries. These particles enter the caterpillar's cells where they induce immunosuppression and control development, allowing the wasp larvae to survive.

Although many examples of symbiotic bacteria are known, the present case of a parasitic species using a virus to control its host's physiology is unique. To improve our understanding of the phenomenon, researchers at the Institut de recherche sur la biologie de l'insecte (CNRS/Université François-Rabelais Tours) are studying these viral particles in detail. In previous work, they had questioned whether the particles were truly viral, as they found that the particle genome lacked the necessary machinery for replication usually found in viruses.

Their most recent findings, published in Science, show that the particles are indeed viral in nature, but that their components lie within the wasp's own genome. More that twenty different genes coding for characteristic components of nudiviruses - insect viruses often used in biological pest control - are expressed in the wasps' ovaries. Furthermore, these genes are conserved in the different kinds of wasp that make these particles.

The results indicate that the ancestor of the braconid wasps integrated the genome of a nudivirus into its own genome. Although these genes continue to produce viral particles, the particles now deliver the wasp's own virulence genes into the parasitized host.

The wasps have therefore "domesticated" a virus to turn it into a vector for transferring their genes. Study of this phenomenon is particularly interesting for the development of new vectors for gene therapy, a therapeutic technique that consists of inserting genes into an individual's cells or tissues to treat an illness. Genes are delivered using a deactivated virus as a vector. The particles from parasite wasps are in fact true "natural" vectors, selected over 100 million years to perform this function and capable of transferring large quantities of genetic material (more than 150 genes). Understanding how they work could therefore be very useful for the design of new therapeutic vectors.