期刊
ELIFE
卷 11, 期 -, 页码 -出版社
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.83840
关键词
mutually exclusive expression; antigenic switching; malaria pathogenesis; immune evasion; gene expression
类别
资金
- National Institute of Allergy and Infectious Diseases [P2BEP3_191777]
- National Institutes of Health
- Swiss National Science Foundation
- [AI 52390]
- [AI99327]
- [T32GM008539]
- [F31AI164897]
- Swiss National Science Foundation (SNF) [P2BEP3_191777] Funding Source: Swiss National Science Foundation (SNF)
Malaria parasites use transcriptional control and a gene network anchored by var2csa to coordinate switching of antigen exposure and maintain chronic infections, despite possessing a small repertoire of variant antigen-encoding genes.
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.
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