Transcriptome and histone epigenome of Plasmodium vivax salivary-gland sporozoites point to tight regulatory control and mechanisms for liver-stage differentiation in relapsing malaria

Vivax Sporozoite Consortium

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish (US)
Pages (from-to)501-513
Number of pages13
JournalInternational Journal for Parasitology
Volume49
Issue number7
DOIs
StatePublished - Jun 1 2019

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Plasmodium vivax
Sporozoites
Salivary Glands
Transcriptome
Histones
Malaria
Liver
Infection
Epigenomics
Histone Code
Schizonts
Latin America
Proteomics
Vertebrates

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Infectious Diseases

Cite this

@article{e799aa3a11c54aa89b7ec9ba8ec8f27a,
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",
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. 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.",
author = "{Vivax Sporozoite Consortium} and Ivo Muller and Jex, {Aaron R.} and Kappe, {Stefan H.I.} and Mikolajczak, {Sebastian A.} and Jetsumon Sattabongkot and Rapatbhorn Patrapuvich and Scott Lindner and Flannery, {Erika L.} and Cristian Koepfli and Lindner, {Scott Eugene} and Anita Lerch and Emery-Corbin, {Samantha J.} and Sarah Charnaud and Jeffrey Smith and Nicolas Merrienne and Swearingen, {Kristian E.} and Moritz, {Robert L.} and Michaela Petter and Duffy, {Michael F.} and Vorada Chuenchob",
year = "2019",
month = "6",
day = "1",
doi = "10.1016/j.ijpara.2019.02.007",
language = "English (US)",
volume = "49",
pages = "501--513",
journal = "International Journal for Parasitology",
issn = "0020-7519",
publisher = "Elsevier Limited",
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TY - JOUR

T1 - Transcriptome and histone epigenome of Plasmodium vivax salivary-gland sporozoites point to tight regulatory control and mechanisms for liver-stage differentiation in relapsing malaria

AU - Vivax Sporozoite Consortium

AU - Muller, Ivo

AU - Jex, Aaron R.

AU - Kappe, Stefan H.I.

AU - Mikolajczak, Sebastian A.

AU - Sattabongkot, Jetsumon

AU - Patrapuvich, Rapatbhorn

AU - Lindner, Scott

AU - Flannery, Erika L.

AU - Koepfli, Cristian

AU - Lindner, Scott Eugene

AU - Lerch, Anita

AU - Emery-Corbin, Samantha J.

AU - Charnaud, Sarah

AU - Smith, Jeffrey

AU - Merrienne, Nicolas

AU - Swearingen, Kristian E.

AU - Moritz, Robert L.

AU - Petter, Michaela

AU - Duffy, Michael F.

AU - Chuenchob, Vorada

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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.

AB - 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.

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U2 - 10.1016/j.ijpara.2019.02.007

DO - 10.1016/j.ijpara.2019.02.007

M3 - Article

VL - 49

SP - 501

EP - 513

JO - International Journal for Parasitology

JF - International Journal for Parasitology

SN - 0020-7519

IS - 7

ER -