Saturday, January 3, 2009

Giardia and Coat Switching

Giardiasis in humans is a diarrheal infection of the small intestine by a single-celled organism called Giardia lamblia. In the U.S., 20,000 cases are reported to the CDC annually, but the true annual incidence is estimated at 2 million people. Giardia has a wide range of mammalian hosts besides humans, thus making it very difficult to eradicate.


NYTimes:
Giardia infections can linger for months because the parasite plays a cunning defense against the body’s immune system. In its genomic wardrobe, it has 190 coats to choose from. As soon as the immune system has generated antibodies against one coat, Giardia switches to another. Because of the parasite’s persistence and infectivity, some 280 million cases of giardiasis occur in the world each year, the World Health Organization estimates, though most of these are in developing countries.

Giardia’s offensive game could have a fatal weakness, however. Biologists led by Hugo D. Luján at the Catholic University of Córdoba in Argentina have gained a striking insight into its coat-shuffling stratagem.

With this knowledge, they have accomplished a cunning counterploy: they have forced the parasite to make and wear all its coat proteins at the same time. This altered parasite, they hope, should serve as the perfect vaccine, because it immunizes the body to the full repertoire of Giardia’s coat proteins all at once. The idea has worked well in animal tests, Dr. Luján said.

Each of the parasite’s 190 coat genes is the recipe for making a different protein, and the parasite switches its coat every 10 generations or so. To produce the coat, Giardia does not switch these genes on one at a time, as might be expected. Instead, it seems to leave them all turned on, allowing each to generate a messenger RNA copy of itself. Usually the messenger RNAs would direct the synthesis of proteins, but giardia then destroys all but one of the messengers, and the survivor makes the coat of the day.

To kill its messenger RNAs, Giardia has adapted an ancient cellular system known as RNA interference. The system is designed to destroy foreign RNA, like that of invading viruses, so it was surprising to find it regulating a cell’s own RNAs, Dr. Luján said.

He thinks the same general approach — forcing expression of all coat proteins simultaneously — might help produce vaccines against the other protozoan parasites that rely on coat switching to dodge the immune system. These include malaria and the trypanosomes that cause sleeping sickness and Leishmaniasis.

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