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New insights into the survival and transmission strategy of malaria parasites
Date:8/13/2014

HP1 proteins are found in most eukaryotic organisms and are important regulators of gene silencing. In short, HP1 induces heritable condensation of chromosomal regions. As a result genes located within these regions are not expressed. Importantly, since this conformation is reversible HP1-controlled genes can become activated without requiring changes in the underlying DNA sequence.

The team led by Till Voss at the Swiss Tropical and Public Health Institute in collaboration with colleagues from the Nanyang Technological University in Singapore engineered a mutant parasite in which HP1 expression can be shut down at the push of a button. The researchers observed that in HP1-depleted parasites all of the 60 so-called var genes became highly active.

Each var gene encodes a distinct variant of the virulence factor PfEMP1, which is displayed on the surface of the parasite-infected red blood cell. PfEMP1 is a major target of the immune system in infected humans. Individual parasites normally express only one of the 60 different var/PfEMP1 proteins, while keeping all other members silenced. By switching to another var/PfEMP1 variant the parasite is able to escape existing immune responses raised against previous variants. The new study shows that HP1 protects the PfEMP1 antigenic repertoire from being exposed to the immune system at once.

The new study shows that HP1 protects the PfEMP1 antigenic repertoire from being exposed to the immune system at once. "This finding is a major step forward in understanding the complex mechanisms responsible for antigenic variation," says Till Voss from the Swiss Tropical and Public Health Institute in Basel. "Furthermore, the tools generated in our study may be relevant for future research on malaria vaccines and immunity."

Lack of HP1 triggers production of malaria transmission stages

Importantly, the study also reveals that parasites lacking HP1 fail to copy their genomes and are
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Contact: Christian Heuss
christian.heuss@unibas.ch
41-612-848-683
Swiss Tropical and Public Health Institute
Source:Eurekalert

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