Title | A coordinated transcriptional switching network mediates antigenic variation of human malaria parasites. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Zhang X, Florini F, Visone JE, Lionardi I, Gross MR, Patel V, Deitsch KW |
Journal | Elife |
Volume | 11 |
Date Published | 2022 Dec 14 |
ISSN | 2050-084X |
Keywords | Animals, 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. |
DOI | 10.7554/eLife.83840 |
Alternate Journal | Elife |
PubMed ID | 36515978 |
PubMed Central ID | PMC9833823 |
Grant List | F31 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 |
Submitted by ljc4002 on August 21, 2025 - 2:12pm