Malaria's secret weapon revealed

Apr 10 2005

A US-led international team of scientists have discovered how the deadliest malaria parasite is able to "hide" from the body's immune system.

The research team, scientists from the Howard Hughes Medical Institute in Maryland and the Weatherall Institute of Molecular Medicine, Oxford, says that a parasite, Plasmodium falciparum, constantly changes the appearance of a protein it deposits on infected cells.

Professor Chris Newbold, Weatherall Institute of Molecular Medicine says it has evolved to have a long life because it has to be around long enough to live in a mosquito before it is transmitted to a human and it does this by continuously changing the version of a protein known as PfEMP1 that it deposits on the surface of infected cells.

This means the human immune system does not have enough time to begin making antibodies against the protein before the parasite changes its appearance. The team says the discovery could lead to new avenues for drug research.

Malaria causes more than 300 million acute illnesses and at least one million deaths each year, most of them in developing countries.

Professor Chris Newbold says it has evolved to have a long life because it has to be around long enough to live in a mosquito before it is transmitted to a human and it does this by continuously changing the version of a protein known as PfEMP1 that it deposits on the surface of infected cells and says as yet not enough is understood about the mechanics of the parasite.

Scientists already knew that a family of genes known as var controls the production of PfEMP1, and the malaria parasite's genome contains at least 50 var genes, but only one is expressed at any given time, giving rise to a single version of the PfEMP1 protein.

During the course of an infection, expression switches from one var gene to another, and all the rest are silenced.The teams investigated why that happens and found there were differences in the DNA of "silent" and "active" var genes. In silent genes, a protein called silent information regulator 2 (SIR2) plays a role in "muting" the DNA, and there is also a mechanism in the genome which moves the selected var gene into a "spotlight" so it becomes active. Finding out more about the mechanism by which the var genes are switched on or off could lead to the development of new drugs for malaria.

Dr Alan Cowman of the Howard Hughes Medical Institute in Maryland, who led the research, says if a way could be found to cause the parasite to switch all the var genes on, then the body would see all the variations of var genes, and the immune system would be able to control the infection.

The research was a useful step in the right direction, but that there was not enough information yet to develop medicines says Professor Chris Newbold.