- •Use of in vivo Plasmodium vivax model to study latent liver infections.
- •Use of the MMV048 drug to selectively kill replicating liver parasites.
- •Proteome of human hepatocyte-specific EVs present in a complex biofluid.
- •EVs from this model contain parasite proteins, one exclusively associated with hypnozoites.
Abbreviations:AEpS (abundance estimated per sample), D8 (Day 8 postinfection), D21 (Day 21 postinfection), DMSO (Dimethyl sulfoxide), EVs (Extracellular vesicles), FRG KO (FRG huHEP) (C57Bl/6 mice with a triple mutation (FAH−/−Rag2−/−IL2Rγnull) and repopulated with primary human hepatocytes), ID (identifier), IFA (Immunofluorescence assay), IV (intravenous infection), MB (mosquito bite), PI4K (phosphatidylinositol kinase), PIK3C2B (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta), PR (protein ratio), SEC (size-exclusion chromatography), TBS (Tris-buffered saline), TQ (tafenoquine)
- Robinson L.J.
- Wampfler R.
- Betuela I.
- Karl S.
- White M.T.
- Li Wai Suen C.S.
- et al.
- Martin-Jaular L.
- de Menezes-Neto A.
- Monguio-Tortajada M.
- Elizalde-Torrent A.
- Diaz-Varela M.
- Fernandez-Becerra C.
- et al.
Experimental Design and Statistical Rationale
P. vivax Infection of FRG huHEP Mice
18S qRT-PCR Analysis of Parasite Load
Isolation of EVs
Liquid Chromatography Tandem Mass Spectrometry
Mass Spectrometry Data Analysis
P. vivax Hypnozoite Biomarker Discovery
Human Proteome of Plasma-Derived EVs From P. vivax-Infected FRG huHEP Mice
Identification of P. vivax Hypnozoites Biomarkers Associated to Plasma-Derived EVs in the FRG huHEP Mice
Conflict of interest
Funding and additional information
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- Supplementary Table 1
- Supplementary Table 2
- Supplementary Table 3
- Supplementary Table 4
- Supplementary Table 5
- Supplementary Table 6
- Supplementary Table 7
- Supplementary Table 8
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Present address for Melisa Gualdrón-López: School of Public Health, University of Alberta, Edmonton, Canada.
Present address for Miriam Díaz-Varela: Department of Biochemistry, WHO Collaborative Center for Research and Training in Immunology, University of Lausanne, Epalinges, Vaud, Switzerland.
Present address for Ryan W.J. Steel: The Water and Eliza Hall Institute of Medical Research, Division of Infection and Immunity, Australia.
Present address for Carola Schäfer: Evotec, Hamburg, Germany.
Present address for Vorada Chuenchob: Novartis Institute for Tropical Diseases, Emeryville, USA.
Present address for Sebastian A. Mikolajczak: Novartis Institute for Tropical Diseases, Emeryville, USA.
Present address for Erika L. Flannery: Novartis Institute for Tropical Diseases, Emeryville, USA.
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