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Plasmodium, the parasite responsible for malaria, infects red blood cells. It produces proteins in the red blood cells that bind to the surface of the host cell. These are known as adhesion proteins. They prevent the red blood cells from circulating correctly in the blood capillaries, and trigger the symptoms of severe malaria. The parasite has 60 genes coding for 60 different adhesion proteins, only one of which appears on the surface of the red blood cell at any one time. In this way the various adhesion proteins are presented in turn, and the parasite keeps one step ahead of the host's immune system, which must learn to recognize and then destroy infected cells.
Scientists in the team led by Artur Scherf (Institut Pasteur, CNRS) discovered this previously unknown mechanism used by the Plasmodium parasite to outmaneuver the immune system time and time again. The scientists showed that an enzyme-type protein, known as RNase, is at the root of the process: it destroys the nascent messenger RNA of genes coding for adhesion proteins, allowing only one of the 60 types of adhesion molecule to be expressed on the surface of the infected red blood cell. Following infection in humans, the parasite will continually express different new adhesion proteins in turn, giving the antibodies of the immune system no time to learn to recognize each one. This process is known as antigenic variation. The mechanism of this newly discovered gene regulation system has never before been observed, and is highly likely to be found in other organisms.
This work was published in Nature on Sunday June 29, 2014, and contributes to a better understanding of the virulence mechanisms employed by the parasite. The next stage for the scientists will be to try to explain what influences the choice of expression of a certain gene at any given time. The team's long-term objective is to find a treatment to block this mechanism whereby the deadly pathogen evades the immune system.
Illustration : © Institut Pasteur/Artur Scherf - Aurélie Claes
Electron microscopy of a red blood cell infected by Plasmodium
Exonuclease-mediated degradation of nascent RNA silences genes linked to severe malaria, Nature, June 29, 2014, DOI: http://dx.doi.org/10.1038/nature13468