Alternative Invasion Mechanisms and Host Immune Response to Plasmodium vivax Malaria: Trends and Future Directions

Kepple, Daniel; Pestana, Kareen; Tomida, Junya; Abebe, Abnet; Golassa, Lemu; Lo, Eugenia

doi:10.20944/preprints202011.0689.v1

Cited by 4 publications

(2 citation statements)

References 158 publications

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“…Our previously published whole genome sequence data identified several mutations and structural polymorphisms in genes from the PvEBP, PvRBP, PvMSP, and PvTRAg gene families that are likely to involve in erythrocyte invasion (9). Specific binding regions in some of the genes such as PvDBP1, PvEBP/DBP2, PvRBP2b, and PvMSP3 have been identified (44). To further explore the putative function, we compared relative expression levels of 43 erythrocyte binding gene candidates (Supplementary Table 1) in the 10 Ethiopian P. vivax samples with other geographical isolates that were of majority schizont stage.…”

Section: Data Analysesmentioning

confidence: 99%

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

Kepple

Ford

Williams

et al. 2023

Preprint

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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 PvRBP2a and PvRBP3 expressed six-fold higher than PvDBP1and 60-fold higher than PvEBP/DBP2. 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., PvDBP1 and PvEBP/DBP2 were highly expressed in the Cambodian but not the Brazilian and Ethiopian isolates, whereas PvRBP2a and PvRBP2b showed higher expression in the Ethiopian and Cambodian than the Brazilian isolates. Compared to Pvs25, 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.

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Section: Data Analysesmentioning

confidence: 99%

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

Kepple

Ford

Williams

et al. 2023

Preprint

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“…Furthermore, P. vivax and P. ovale's unique ability to form dormant stage hypnozoites complicates parasite clearance and can reintroduce old parasite strains into transmission reservoirs [2,19]. Gametocytes are critical for malaria transmission and possible immune evasion in both the human and mosquito hosts [29,30], emphasizing the importance of accurate detection. This chapter aims to provide a systemic review that highlights the complexity of Plasmodium gametocytes at the biological and genetic levels and current methods used to track and detect Plasmodium gametocytes.…”

Section: Development and Transmission Of Plasmodiummentioning

confidence: 99%

From Genes to Biomarkers: Understanding the Biology of Malaria Gametocytes and Their Detection

Kepple¹,

Ford²,

Little³

et al. 2022

Genetic Polymorphisms - New Insights

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Each year, approximately 230 million malaria cases and 400,00 malaria deaths are reported worldwide. Malaria is a life-threatening disease caused by Plasmodium parasites that are transmitted from one individual to another through the bites of infected female Anopheles mosquitoes. Malaria parasites replicate asexually in the human host, and, in each replication cycle, a portion of the asexual stages develops into sexual gametocytes that permit transmission. The proportion of infections that carries gametocytes and the infectivity of gametocytes are indicators of human-to-mosquito transmission potential. In P. falciparum, gametocytes appear 10–14 days after infection, whereas in P. vivax gametocytes appear simultaneously with asexual schizonts. Such difference in development not only increases the length of time that an individual is infectious, but also increases the likelihood of transmission before treatment. The conversion from asexual parasites to gametocytes is also highly variable between infections. Differences in age, host immune response, parasite genetic composition, density of red blood cells, presence of co-infecting parasite strains, and antimalarial drug use could affect gametocytes production. In P. vivax, the unique ability to produce hypnozoites, a dormant liver stage of the parasite, may allow gametocytes to be produced periodically from relapse and contribute to transmission. In this chapter, we will provide an overview of the biology of Plasmodium gametocytes, existing tools for gametocyte detection, and features of gametocyte genes. The biological insights and genetic findings are essential to developing better detection biomarkers and effective strategies to reduce transmission in malaria-endemic countries.

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Copy number variations ofPlasmodium vivax DBP1,EBP/DBP2, andRBP2bin Duffy-positive and Duffy-negative Ethiopians

Pestana,

Ford,

Rama

et al. 2024

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Recent evidence challenges the belief that Duffy-negative individuals are resistant to Plasmodium vivax due to lacking Duffy Antigen Receptor for Chemokines (DARC). Erythrocyte Binding Protein (EBP/DBP2) has shown moderate binding to Duffy-negative erythrocytes in vitro. Reticulocyte Binding Protein 2b (RBP2b) interactions with Transferrin Receptor 1 (TfR1) suggest involvement in Duffy-negative infections. Gene copy number variations in PvDBP1, PvEBP/DBP2, and PvRBP2b were investigated in Duffy-positive and Duffy-negative P. vivax-infected individuals from Ethiopia. Among Duffy-positive samples, 34% displayed PvDBP1 duplications (Cambodian-type). In Duffy-negative infections, 30% showed duplications, mostly Cambodian-type. For PvEBP/DBP2 and PvRBP2b, Duffy-positive samples exhibited higher duplication rates (1-8 copies for PvEBP/DBP2, 1-5 copies for PvRBP2b 46% and 43% respectively) compared to Duffy-negatives (20.8% and 26% respectively). The range of copy number variations was lower in Duffy-negative infections. Demographic and clinical factors associated with gene multiplications in both Duffy types were explored, enhancing understanding of P. vivax evolution in Duffy-negative Africans.

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Alternative Invasion Mechanisms and Host Immune Response to Plasmodium vivax Malaria: Trends and Future Directions

Cited by 4 publications

References 158 publications

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

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

From Genes to Biomarkers: Understanding the Biology of Malaria Gametocytes and Their Detection

Copy number variations ofPlasmodium vivax DBP1,EBP/DBP2, andRBP2bin Duffy-positive and Duffy-negative Ethiopians

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