Identification of novel PfEMP1 variants containing domain cassettes 11, 15 and 8 that mediate the Plasmodium falciparum virulence-associated rosetting phenotype

• DOI: 10.1371/journal.ppat.1012434
• Publication Date: 2025-01-13T19:04:52Z
• Authors: Florence E. McLean; Brian R. Omondi; Nouhoum Diallo; Stanley Otoboh; Carolyne Kifude; Abdirahman I. Abdi; Rivka Lim; Thomas D. Otto; Ashfaq Ghumra; J. Alexandra Rowe
• Keywords: Rosette (schizont appearance)

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a diverse family of variant surface antigens, encoded by var genes, that mediates binding infected erythrocytes to human cells and plays key role in parasite immune evasion malaria pathology. The increased availability genome sequence data has revolutionised the study PfEMP1 diversity across multiple P . isolates. However, making functional sense genomic relies on ability infer phenotype from gene sequence. For rosetting, uninfected erythrocytes, analysis gene/PfEMP1 sequences encoding limited, with only eight rosette-mediating variants described date. These known rosetting fall into two types, characterised N-terminal domains as “domain cassette” 11 (DC11) DC16. Here we test hypothesis DC11 DC16 are types mediate examining set thirteen recent culture-adapted Kenyan lines. We first analysed repertoires lines identified an average three or per genotype. In vitro rosette selection yielded four high frequency, their transcription, expression, disruption function novel variants. Two these were predicted type (one showing dual rosetting/IgM-Fc-binding phenotype), whereas contained DC15 (DBLα1.2-CIDRα1.5b) not previously associated rosetting. also showed Thai line expressing DC8-like binds form rosettes. Hence, expand current knowledge mechanisms emphasize mediating more than recognised.