Back to Search
Start Over
Antigenic variation in Plasmodium falciparum malaria involves a highly structured switching pattern
- Source :
- PLoS Pathogens, Vol 7, Iss 3, p e1001306 (2011), PLoS Pathogens
- Publication Year :
- 2011
- Publisher :
- Public Library of Science (PLoS), 2011.
-
Abstract
- Many pathogenic bacteria, fungi, and protozoa achieve chronic infection through an immune evasion strategy known as antigenic variation. In the human malaria parasite Plasmodium falciparum, this involves transcriptional switching among members of the var gene family, causing parasites with different antigenic and phenotypic characteristics to appear at different times within a population. Here we use a genome-wide approach to explore this process in vitro within a set of cloned parasite populations. Our analyses reveal a non-random, highly structured switch pathway where an initially dominant transcript switches via a set of switch-intermediates either to a new dominant transcript, or back to the original. We show that this specific pathway can arise through an evolutionary conflict in which the pathogen has to optimise between safeguarding its limited antigenic repertoire and remaining capable of establishing infections in non-naïve individuals. Our results thus demonstrate a crucial role for structured switching during the early phases of infections and provide a unifying theory of antigenic variation in P. falciparum malaria as a balanced process of parasite-intrinsic switching and immune-mediated selection.<br />Author Summary The malaria parasite Plasmodium falciparum avoids recognition and clearance by the immune system by sequentially switching between members of the var multi-gene family which encode the immunodominant surface proteins PfEMP1. However, some mechanism must exist to prevent rapid exposure of the pathogen's entire antigenic repertoire as this would quickly terminate the infection. It has previously been shown that the immune system can play an important role in orchestrating the sequential display of variants once an infection is established; however this does not explain how repertoire exhaustion is avoided in the initial phases of infection before an immune response has been established. Here we show that P. falciparum has evolved a highly structured switching pattern to prevent repertoire exhaustion in the early stages of infection without compromising the ability to establish new infections among partially immune individuals.
- Subjects :
- Infectious Diseases/Epidemiology and Control of Infectious Diseases
Transcription, Genetic
QH301-705.5
030231 tropical medicine
Immunology
Population
Plasmodium falciparum
Protozoan Proteins
Antigens, Protozoan
Microbiology
Plasmodium
03 medical and health sciences
0302 clinical medicine
Virology
parasitic diseases
Genetics
Antigenic variation
medicine
Gene family
Malaria, Falciparum
Biology (General)
education
Pathogen
Molecular Biology
030304 developmental biology
0303 health sciences
education.field_of_study
biology
Gene Expression Profiling
RC581-607
biology.organism_classification
medicine.disease
Antigenic Variation
3. Good health
Phenotype
Infectious Diseases
Protozoa
Parasitology
Immunologic diseases. Allergy
Malaria
Algorithms
Research Article
Infectious Diseases/Tropical and Travel-Associated Diseases
Subjects
Details
- Language :
- English
- ISSN :
- 15537374 and 15537366
- Volume :
- 7
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- PLoS Pathogens
- Accession number :
- edsair.doi.dedup.....70e1f37cd64868428b3eb250b1799c56