Download Malaria parasites use antigenic variation to avoid immune clearance

IS ANTIGENIC VARIATION IN PLASMODIUM FALCIPARUM REGULATED BY
NUCLEAR ARCHITECTURE?
Stuart A. Ralph*, Lucio H. Freitas-Junior*, Rosaura Hernandez-Rivas† and Artur Scherf*.
* Institut Pasteur, Biology of Host Parasite Interaction Unit-CNRS URA2581, 25 rue du Dr. Roux, 75724
Paris, France.
†
Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del IPN,
Apartado Postal 14-740, 07360, México, D. F., México.
Malaria parasites use antigenic variation to avoid immune clearance and increase the duration of
infection in the human host. Variation at the surface of P. falciparum-infected erythrocytes is mediated
by the differential control of a family of surface antigens encoded by var genes. Switching of var gene
expression occurs in situ, mostly from telomere-associated loci, without detectable DNA alterations,
suggesting that it is controlled by epigenetic changes. We have identified specific modifications in
chromatin that effect the activity of var gene promoters. One type of modification is mediated by a
protein homologous to yeast Sir2 called PfSir2, which influences heterochromatin structure through
histone hypoacetylation. Upon activation of a specific telomere-associated var gene, PfSir2 is removed
from the promoter region and acetylation of histone H4 occurs. FISH analysis of active and inactive var
genes also demonstrates that the transcription of var genes is facilitated by positional changes within
the nucleus. We conclude that dynamic remodeling of chromatin and intranuclear positioning control
antigenic variation in P. falciparum