CD98hc polymorphism and risk of Plasmodium vivax malaria in Amazonians

• Grant number: 25/07859-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2025
• End date: November 30, 2029
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Marcelo Urbano Ferreira
• Grantee: Kaitlyn Marie Dalrymple
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 24/04280-2 - Exploring the dual role of CD98hc in human erythropoiesis and Vivax Malaria, AP.TEM

Abstract

Malaria remains a significant global health issue, with Plasmodium vivax responsible for 72% of cases in the Americas, particularly in Brazil's Amazon Basin, where genetic diversity in an admixed population may influence malaria susceptibility. This study aims to test whether polymorphisms in the SLC3A2 gene affect P. vivax infection risk by analyzing genetic variants in the town of Mâncio Lima, Brazil, a hot spot for vivax malaria infection, using Sanger sequencing and molecular genotyping. The SLC3A2 gene codes for the reticulocyte surface protein CD98hc, which allows parasite invasion of the cell by acting as a ligand receptor for the reticulocyte-binding protein PvRBP2a. This study will also investigate whether naturally acquired antibodies to PvRBP2a inhibit parasite entry into reticulocytes, especially in individuals with SLC3A2 polymorphisms that reduce PvRBP2a-binding affinity. The study involves biological samples collected from two separate studies: those from cross-sectional surveys (2018-2021) will be used to characterize SLC3A2 gene variants; and those from a therapeutic efficacy study of chloroquine-primaquine (2014-2015) will be used to test for anti-PvRBP2a antibodies. Statistical methods like regression models and mixed models will be used to assess malaria risk. Additionally, a 12-month research internship at the Pasteur Institute will be undertaken to insert SLC3A2 polymorphisms into human erythroid precursors to engraft and assess their impact on erythropoiesis and P. vivax infection in humanized mice, a means of validation of the results from the first objective. This research will contribute to understanding genetic factors influencing malaria susceptibility in the Amazon, offering insights into potential interventions and treatment strategies. (AU)