Abstract
BACKGROUND: Plasmodium vivax rosetting is a cytoadhesion phenomenon associated with parasite virulence and clinical manifestations of malaria. However, the molecular mechanisms underlying this process remain poorly understood. Comparative transcriptomic analysis between isolates with different rosetting capacities may provide insights into the molecular base and clinical outcome of parasite populations with distinct rosetting characteristics. OBJECTIVES: Our study aims to identify and describe the transcription profile of P. vivax isolates with high and low rosetting rates. METHODS: We used RNA-seq to compare the transcriptomes of 10 field P. vivax isolates from the Brazilian Amazon. FINDINGS: Among the 492 differentially expressed genes of P. vivax isolates with high rosetting (HR) versus low rosetting (LR) formation, 172 (34,96%) are annotated as genes conserved within Plasmodium and of unknown function. The expression profiles of the other 320 genes (65,04%) highlight the importance of integral membrane proteins and membrane-associated proteins with adhesive or adhesin-like properties, representing 10% of the transcribed genes (53 genes), such as Plasmodium Helical Interspersed Sub-telomeric (PHIST) proteins in rosetting phenotypes. Transcriptomic analyses revealed that approximately 4% (19 genes) of differentially expressed genes were kinases and 50% (248 genes) other proteins. Among cell surface proteins and integral/membrane-associated proteins, differentiated expression and positive regulation of representative 6-cysteine gene family were observed in HR formation group, which includes a tryptophan-rich protein (TRAG16), the 41K blood stage antigen precursor 41-3 protein, and merozoite surface protein 7-like (MSP7-like). MAIN CONCLUSIONS: These results contribute to understanding the molecular basis of P. vivax rosetting.