Related Experiment Videos
Variable var transition rates underlie antigenic variation in malaria
Paul Horrocks1, Robert Pinches, Zóe Christodoulou
1Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom. horrocks@hammer.imm.ox.ac.uk
Summary
Antigenic variation in Plasmodium falciparum is driven by var gene switching. This study quantifies var gene on/off rates, revealing they are intrinsic properties that regulate immune evasion and chronic infection.
Area of Science:
- Malariology
- Molecular Parasitology
- Immunology
Background:
- Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) mediates cytoadhesion and immune evasion.
- Antigenic variation through PfEMP1 switching, encoded by the var gene family, enables chronic infection.
- Regulation of var gene transcriptional switching remains poorly understood.
Purpose of the Study:
- To measure the transition on and off rates for var gene variants.
- To investigate the factors influencing var gene switching.
- To understand the regulation of antigenic variation in Plasmodium falciparum.
Main Methods:
- Measurement of transition on and off rates for var gene variants.
- Analysis of rate variations among different var gene variants.
- Comparison of rates in isogenic clones expressing the same var gene.
Main Results:
- On and off rates for var gene variants are dissimilar and vary significantly between variants.
- For isogenic clones, on and off rates are constant, suggesting an intrinsic property of the gene.
- Evidence suggests DNA surrounding var genes influences their activation/silencing probability.
- Recent expression history can disallow certain variant transitions.
Conclusions:
- Var gene switching rates are intrinsic and regulated by surrounding DNA.
- These regulated transitions are crucial for Plasmodium falciparum's immune evasion.
- Understanding var gene regulation offers insights into chronic malaria infections.