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© Artur Scherf
Scanning Electron Microscopy of Red Blood Cell infected by Plasmodium falciparum.
Publication : Cell host & microbe

In Vitro Culture, Drug Sensitivity, and Transcriptome of Plasmodium Vivax Hypnozoites

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cell host & microbe - 22 Feb 2018

Gural N, Mancio-Silva L, Miller AB, Galstian A, Butty VL, Levine SS, Patrapuvich R, Desai SP, Mikolajczak SA, Kappe SHI, Fleming HE, March S, Sattabongkot J, Bhatia SN

Link to Pubmed [PMID] – 29478773

Cell Host Microbe 2018 Mar;23(3):395-406.e4

The unique relapsing nature of Plasmodium vivax infection is a major barrier to malaria eradication. Upon infection, dormant liver-stage forms, hypnozoites, linger for weeks to months and then relapse to cause recurrent blood-stage infection. Very little is known about hypnozoite biology; definitive biomarkers are lacking and in vitro platforms that support phenotypic studies are needed. Here, we recapitulate the entire liver stage of P. vivax in vitro, using a multiwell format that incorporates micropatterned primary human hepatocyte co-cultures (MPCCs). MPCCs feature key aspects of P. vivax biology, including establishment of persistent small forms and growing schizonts, merosome release, and subsequent infection of reticulocytes. We find that the small forms exhibit previously described hallmarks of hypnozoites, and we pilot MPCCs as a tool for testing candidate anti-hypnozoite drugs. Finally, we employ a hybrid capture strategy and RNA sequencing to describe the hypnozoite transcriptome and gain insight into its biology.

https://www.ncbi.nlm.nih.gov/pubmed/29478773