Comparative transcriptomics reveal differential gene expression in Plasmodium vivax geographical isolates and implications on erythrocyte invasion mechanisms.

Plasmodium vivax uses 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 to P. vivax . In recent years, P. vivax malaria 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 American P. vivax are well documented, the gene expression profile of P. vivax in Africa and more specifically the expression level of several erythrocyte binding gene candidates as compared to DBP1 are largely unknown. This paper characterized the first P. vivax transcriptome 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 Cambodian P. vivax being most similar. Majority of the gene transcripts involved in protein transportation, housekeeping, and host interaction were highly transcribed in the Ethiopian P. vivax . Erythrocyte binding genes including PvRBP 2a and PvRBP 3 expressed six-fold higher than PvDBP 1and 60-fold higher than PvEB P/ DBP 2. Other genes including PvRBP1a, PvMSP3.8 , PvMSP3.9 , PvTRAG2, PvTRAG14, and PvTRAG22 also showed relatively high expression. Differential expression was observed among geographical isolates, e.g., PvDBP 1 and PvEB P/ DBP 2 were highly expressed in the Cambodian but not the Brazilian and Ethiopian isolates, whereas PvRBP 2a and PvRBP 2b showed higher expression in the Ethiopian and Cambodian than the Brazilian isolates. Compared to Pvs 25, the standard biomarker for detecting female gametocytes, PvAP2-G (PVP01_1440800), GAP (PVP01_1403000), and Pvs47 (PVP01_1208000) were highly expressed across geographical samples. These findings provide an important baseline for future comparisons of P. vivax transcriptomes from Duffy-negative infections and highlight potential biomarkers for improved gametocyte detection.
Competing Interests: Potential conflicts of interest. The authors declare no conflict of interest.