A coordinated transcriptional switching network mediates antigenic variation of human malaria parasites.

TitleA coordinated transcriptional switching network mediates antigenic variation of human malaria parasites.
Publication TypeJournal Article
Year of Publication2022
AuthorsZhang X, Florini F, Visone JE, Lionardi I, Gross MR, Patel V, Deitsch KW
JournalElife
Volume11
Date Published2022 Dec 14
ISSN2050-084X
KeywordsAnimals, Antigenic Variation, Antigens, Humans, Malaria, Malaria, Falciparum, Parasites, Plasmodium falciparum, Protozoan Proteins
Abstract

Malaria parasites avoid immune clearance through their ability to systematically alter antigens exposed on the surface of infected red blood cells. This is accomplished by tightly regulated transcriptional control of individual members of a large, multicopy gene family called var and is the key to both the virulence and chronic nature of malaria infections. Expression of var genes is mutually exclusive and controlled epigenetically, however how large populations of parasites coordinate var gene switching to avoid premature exposure of the antigenic repertoire is unknown. Here, we provide evidence for a transcriptional network anchored by a universally conserved gene called var2csa that coordinates the switching process. We describe a structured switching bias that shifts overtime and could shape the pattern of var expression over the course of a lengthy infection. Our results provide an explanation for a previously mysterious aspect of malaria infections and shed light on how parasites possessing a relatively small repertoire of variant antigen-encoding genes can coordinate switching events to limit antigen exposure, thereby maintaining chronic infections.

DOI10.7554/eLife.83840
Alternate JournalElife
PubMed ID36515978
PubMed Central IDPMC9833823
Grant ListF31 AI164897 / AI / NIAID NIH HHS / United States
R01 AI138499 / AI / NIAID NIH HHS / United States
R01 AI161299 / AI / NIAID NIH HHS / United States
T32 GM008539 / GM / NIGMS NIH HHS / United States

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