Antigenic variation in Plasmodium falciparum.
The persistence of the human malaria parasite Plasmodium falciparum during blood stage proliferation in its host depends on the successive expression of variant molecules at the surface of infected erythrocytes. This variation is mediated by the differential control of a family of surface molecules termed PfEMP1 encoded by approximately 60 var genes. Each individual parasite expresses a single var gene at a time, maintaining all other members of the family in a transcriptionally silent state. PfEMP1/var enables parasitized erythrocytes to adhere within the microvasculature, resulting in severe disease. This review highlights key regulatory mechanisms thought to be critical for monoallelic expression of var genes. Antigenic variation is orchestrated by epigenetic factors including monoallelic var transcription at separate spatial domains at the nuclear periphery, differential histone marks on otherwise identical var genes, and var silencing mediated by telomeric heterochromatin. In addition, controversies surrounding var genetic elements in antigenic variation are discussed.
Scherf
Artur
A
Biology of Host-Parasite Interactions Unit, CNRS URA2581, Institut Pasteur 75724 Paris, France. ascherf@pasteur.fr
Lopez-Rubio
Jose Juan
JJ
Riviere
Loïc
L
D000818:Animals; D000940:Antigenic Variation; D000953:Antigens, Protozoan / Q000235:genetics*; D044127:Epigenesis, Genetic; D004912:Erythrocytes / Q000469:parasitology; D020868:Gene Silencing; D017125:Genes, Protozoan; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D008954:Models, Biological; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D016615:Telomere / Q000235:genetics
D000953:Antigens, Protozoan; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum