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Title: In Vitro Culture, Drug Sensitivity, and Transcriptome of Plasmodium Vivax Hypnozoites
Authors: Nil Gural
Liliana Mancio-Silva
Alex B. Miller
Ani Galstian
Vincent L. Butty
Stuart S. Levine
Rapatbhorn Patrapuvich
Salil P. Desai
Sebastian A. Mikolajczak
Stefan H.I. Kappe
Heather E. Fleming
Sandra March
Jetsumon Sattabongkot
Sangeeta N. Bhatia
Massachusetts Institute of Technology
Brigham and Women's Hospital
Mahidol University
Howard Hughes Medical Institute
Broad Institute
Phenomyx LLC
Koch Institute for Integrated Cancer Research at Massachusetts Institue of Technology
Center for Infectious Disease Research
Keywords: Immunology and Microbiology
Issue Date: 14-Mar-2018
Citation: Cell Host and Microbe. Vol.23, No.3 (2018), 395-406.e4
Abstract: © 2018 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. Plasmodium vivax hypnozoites are difficult to study due to the lack of human liver platforms. Gural et al. recapitulated the entire liver stage of P. vivax in vitro, including formation and reactivation of hypnozoites and release of merosomes. Hybrid capture followed by RNA-seq revealed a first look into the hypnozoite transcriptome.
ISSN: 19346069
Appears in Collections:Scopus 2018

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