A coordinated transcriptional switching network mediates antigenic variation of human malaria parasites
- Weill Cornell Medicine, United States
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.
Data availability
Whole genome sequence and transcriptome data are available at the BioProject database of the NCBI. The genome sequencing data can be accessed at this link: http://www.ncbi.nlm.nih.gov/bioproject/515738. The RNAseq data can be accessed at this link: https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA802886.
Article and author information
Author details
Funding
National Institute of Allergy and Infectious Diseases (AI 52390)
- Kirk W Deitsch
National Institute of Allergy and Infectious Diseases (AI99327)
- Kirk W Deitsch
National Institutes of Health (T32GM008539)
- Joseph E Visone
Swiss National Science Foundation (P2BEP3_191777)
- Francesca Florini
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Olivier Silvie, Sorbonne Université, UPMC Univ Paris 06, INSERM, CNRS, France
Version history
- Preprint posted: September 30, 2022 (view preprint)
- Received: September 30, 2022
- Accepted: December 13, 2022
- Accepted Manuscript published: December 14, 2022 (version 1)
- Version of Record published: January 11, 2023 (version 2)
Copyright
© 2022, Zhang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A coordinated transcriptional switching network mediates antigenic variation of human malaria parasites
eLife 11:e83840.
https://doi.org/10.7554/eLife.83840
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