Decoding the impact of nuclear organization on antigenic variation in parasites

Antigenic variation as a strategy to evade the host adaptive immune response has evolved in divergent pathogens. Antigenic variation involves restricted, and often mutually exclusive,

expression of dominant antigens and a periodic switch in antigen expression during infection. In eukaryotes, nuclear compartmentalization, including three-dimensional folding of the genome

and physical separation of proteins in compartments or condensates, regulates mutually exclusive gene expression and chromosomal translocations. In this Review, we discuss the impact of

nuclear organization on antigenic variation in the protozoan pathogens Trypanosoma brucei and Plasmodium falciparum. In particular, we highlight the relevance of nuclear organization in both

mutually exclusive antigen expression and genome stability, which underlie antigenic variation.

We thank all members of the Siegel lab for valuable discussion and ScI-llustrations Carolin Wedel Grafikdesign for help with the figure design. A.B.-S. is funded through the CRC 1064

(213249687), an ERC Starting Grant (3D_Tryps 715466), and an ERC Consolidator Grant (SwitchDecoding 101044320) awarded to T.N.S. M.C. is a Wellcome Investigator (217138/Z/19/Z). Work on this

Review has been supported by funds from the University of Cambridge and LMU München strategic partnership scheme.

Division of Experimental Parasitology, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität München, Munich, Germany

Biomedical Center, Division of Physiological Chemistry, Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany

Department of Biochemistry, University of Cambridge, Cambridge, UK

A.B.-S. and T.N.S conceived the main ideas for the Review. A.B.-S. wrote the original draft. A.B.-S., M.C. and T.N.S. reviewed and edited the paper. T.N.S. prepared the figures.

Nature Microbiology thanks Mohamed-Ali Hakimi and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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