Repurposing of Plasmodium falciparum var genes beyond the blood stage

ElsevierVolume 70, December 2022, 102207Current Opinion in MicrobiologyHighlights•

Plasmodium genomes harbor variant multigene families with diverse functions.

Immunovariant PfEMP1 adhesins, encoded by var genes, play key roles in bloodstage .

Multiple resetting of var gene transcription during the life cycle.

PfEMP1 surface expression in sporozoites points to additional roles in transmission.

Stage-specific regulation of var gene expression may enable functional repurposing.

A commonly observed survival strategy in protozoan parasites is the sequential expression of clonally variant-surface antigens to avoid elimination by the host’s immune response. In malaria-causing P. falciparum, the immunovariant erythrocyte-membrane protein-1 (PfEMP1) adhesin family, encoded by var genes, is responsible for both antigenic variation and cytoadherence of infected erythrocytes to the microvasculature. Until recently, the biological function of these variant genes was believed to be restricted to intraerythrocytic developmental stages. With the advent of new technologies, var gene expression has been confirmed in transmission and pre-erythrocytic stages. Here, we discuss how repurposing of var gene expression beyond chronic blood-stage infection may be critical for successful transmission.

© 2022 The Author(s). Published by Elsevier Ltd.

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