Transcriptome and histone epigenome of Plasmodium vivax salivary-gland sporozoites point to tight regulatory control and potential mechanisms for liver-stage differentiation
Year: 2017
Type: preprint
Abstract: ABSTRACT 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. The salivary-gland sporozoite transcriptome is heavily composed of transcripts associated with functions needed for early infection of the vertebrate host and development within hepatocytes. Through comparisons to recently published proteome data for the P. vivax sporozoite, our study finds that although highly transcribed, these transcripts are not detectable as proteins and may be regulated through translational repression; a finding we test for a small subset of transcripts and proteins through immunofluorescent microscopy of sporozoites and liver stages in humanized mice. We identify 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 largely absent in replicating liver schizonts or mixed blood-stages. Common transcripts up-regulated in sporozoites and hypnozoites compared to mixed (i.e., schizont) liver-stages identify genes linked to dormancy/persistence in bacteria, amoebae and plants. We also characterise histone epigenetic modifications in the P. vivax sporozoite and explore their role in regulating transcription. Collectively, these data support the hypothesis that the sporozoite as a tightly programmed stage primed to infect the human host and identifies potential mechanisms for hypnozoite-formation that may be further explored in liver stage models.
DOI: 10.1101/145250
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 Duffy, Vorada Chuenchob
Institutions: Institut Pasteur, The University of Melbourne, Walter and Eliza Hall Institute of Medical Research, Center for Infectious Disease Research, University of Washington, Pennsylvania State University, Institute for Systems Biology, The Royal Melbourne Hospital, Universitätsklinikum Erlangen, Peter Doherty Institute
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3102056138