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Title: Transcriptome and histone epigenome of Plasmodium vivax salivary-gland sporozoites point to tight regulatory control and mechanisms for liver-stage differentiation in relapsing malaria
Authors: Ivo Muller
Aaron R. Jex
Stefan H.I. Kappe
Sebastian A. Mikolajczak
Jetsumon Sattabongkot
Rapatbhorn Patrapuvich
Scott Lindner
Erika L. Flannery
Cristian Koepfli
Brendan Ansell
Anita Lerch
Samantha J. Emery-Corbin
Sarah Charnaud
Jeffrey Smith
Nicolas Merrienne
Kristian E. Swearingen
Robert L. Moritz
Michaela Petter
Michael F. Duffy
Vorada Chuenchob
Faculty of Veterinary and Agricultural Sciences
Universitätsklinik Erlangen und Medizinische Fakultät
Walter and Eliza Hall Institute of Medical Research
University of Melbourne
Children's Hospital and Regional Medical Center
University of Washington, Seattle
Mahidol University
Institute for Systems Biology
Institut Pasteur, Paris
Pennsylvania State University
Keywords: Immunology and Microbiology;Medicine
Issue Date: 1-Jun-2019
Citation: International Journal for Parasitology. Vol.49, No.7 (2019), 501-513
Abstract: © 2019 Plasmodium vivax is the key obstacle to malaria elimination in Asia and Latin America, largely attributed to its ability to form resilient hypnozoites (sleeper cells) in the host liver that escape treatment and cause relapsing infections. The decision to form hypnozoites is made early in the liver infection and may already be set in sporozoites prior to invasion. To better understand these early stages of infection, we undertook a comprehensive transcriptomic and histone epigenetic characterization of P. vivax sporozoites. Through comparisons with recently published proteomic data for the P. vivax sporozoite, our study found that although highly transcribed, transcripts associated with functions needed for early infection of the vertebrate host are not detectable as proteins and may be regulated through translational repression. We identified differential transcription between the sporozoite and published transcriptomes of asexual blood stages and mixed versus hypnozoite-enriched liver stages. These comparisons point to multiple layers of transcriptional, post-transcriptional and post-translational control that appear active in sporozoites and to a lesser extent hypnozoites, but are largely absent in replicating liver schizonts or mixed blood stages. We also characterised histone epigenetic modifications in the P. vivax sporozoite and explored their role in regulating transcription. Collectively, these data support the hypothesis that the sporozoite is a tightly programmed stage to infect the human host and identify mechanisms for hypnozoite formation that may be further explored in liver stage models.
ISSN: 18790135
Appears in Collections:Scopus 2019

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