Parasites can confuse their hosts' immune system by switching the proteins they display on their surface. But how? The intestinal parasite Giardi lamblia harnesses RNA interference to target which surface proteins to shut down, a study published tomorrow in Nature reports.

"I actually think it's a superb paper," Therdore Nash, chief of gastrointestinal parasitology at the National Institute of Allergy and Infectious Disease, told The Scientist. "It's a very novel and unique mechanism of antigenic variation."

Many important unicellular parasites, including malaria and other species of plasmodium, undergo antigenic variation, in which the parasite can switch which protein is expressed on its membrane surface to confuse and evade the host immune system. These parasites can have 50 to 300 genes encoding this family of surface proteins, but only express one on the surface of each cell at a time. Each parasite has a different mechanism by which they express one protein at a time. To evade the immune system, parasites like Giardia lamblia can spontaneously switch which protein they express. But as opposed to other parasites, Giardia lamblia switches proteins in the absence of a host and for no apparent reason.

To find out the mechanism of this mysterious switching, the researchers, led by Hugo Lujan at the Catholic University of Cordoba, Argentina, examined the transcription of surface protein genes in the parasites' nuclei. They discovered that all but one of the nearly 190 genes encoding for surface proteins (called variant-specific protein-- VSP -- genes) are shut off by RNA interference machinery, including RNA-dependent RNA polymerase, and the RNA cleaving proteins Dicer and Argonaute. By knocking out dicer and RNA polymerase, the cells would express hundreds of proteins on their surface. "We link for the first time the mechanism for RNAi with antigenic variation," Lujan told The Scientist, who was a research fellow in Nash's lab. "That was something that was very surprising."

The next step is to determine what triggers this switch, Lujan said. Work on other parasites indicates that the presence of host immune cells initiates parasite surface protein switching. But since Giardia proteins switch even without the presence of a host, something else might be at work. Lujan is considering the role of epigenetics and how total surface protein expression may affect the switching rate.

Nash pointed out that the surface proteins are not just there to evade host immune cells -- they also help the parasite adhere to host endothelial cells, perhaps suggesting other roles for the protein switching. "We don't' understand it fully," he said, "but it's a great model system for biology."


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