Comparative transcriptomics reveal differential gene expression inPlasmodium vivaxgeographical isolates and implications on erythrocyte invasion mechanisms

AbstractPlasmodium vivaxuses Duffy binding protein (PvDBP1) to bind to the Duffy Antigen-Chemokine Receptor (DARC) to invade human erythrocytes. Individuals who lack DARC expression (Duffy-negative) are thought to be resistance toP. vivax. In recent years,P. vivaxmalaria is becoming more prevalent in Africa with a portion of these cases detected in Duffy-negatives. Apart from DBP1, members of the reticulocyte binding protein (RBP) and tryptophan-rich antigen (TRAg) families may also play a role in erythrocyte invasion. While the transcriptomes of the Southeast Asian and South AmericanP. vivaxare well documented, the gene expression profile ofP. vivaxin Africa and more specifically the expression level of several erythrocyte binding gene candidates as compared to DBP1 are largely unknown. This paper characterized the firstP. vivaxtranscriptome in Africa and compared with those from the Southeast Asian and South American isolates. The expression of 4,404 gene transcripts belong to 12 functional groups including 43 specific erythrocyte binding gene candidates were examined. Overall, there were 10-26% differences in the gene expression profile amongst the geographical isolates, with the Ethiopian and CambodianP. vivaxbeing most similar. Majority of the gene transcripts involved in protein transportation, housekeeping, and host interaction were highly transcribed in the EthiopianP. vivax. Erythrocyte binding genes includingPvRBP2aandPvRBP3expressed six-fold higher thanPvDBP1and60-fold higher thanPvEBP/DBP2. Other genes includingPvRBP1a, PvMSP3.8, PvMSP3.9, PvTRAG2, PvTRAG14, andPvTRAG22also showed relatively high expression. Differential expression was observed among geographical isolates, e.g.,PvDBP1andPvEBP/DBP2were highly expressed in the Cambodian but not the Brazilian and Ethiopian isolates, whereasPvRBP2a andPvRBP2b showed higher expression in the Ethiopian and Cambodian than the Brazilian isolates. Compared toPvs25, the standard biomarker for detecting female gametocytes,PvAP2-G(PVP01_1440800), GAP (PVP01_1403000), andPvs47(PVP01_1208000) were highly expressed across geographical samples. These findings provide an important baseline for future comparisons ofP. vivaxtranscriptomes from Duffy-negative infections and highlight potential biomarkers for improved gametocyte detection.