Disruption of Toxoplasma gondii-Induced Host Cell DNA Replication Is Dependent on Contact Inhibition and Host Cell Type

Edwin Pierre-Louis, Menna G. Etheridge, Rodrigo de Paula Baptista, Asis Khan, Nathan M. Chasen, Ronald D. Etheridge

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The protozoan Toxoplasma gondii is a highly successful obligate intracellular parasite that, upon invasion of its host cell, releases an array of host-modulating protein effectors to counter host defenses and further its own replication and dissemination. Early studies investigating the impact of T. gondii infection on host cell function revealed that this parasite can force normally quiescent cells to activate their cell cycle program. Prior reports by two independent groups identified the dense granule protein effector HCE1/ TEEGR as being solely responsible for driving host cell transcriptional changes through its direct interaction with the cyclin E regulatory complex DP1 and associated transcription factors. Our group independently identified HCE1/TEEGR through the presence of distinct repeated regions found in a number of host nuclear targeted parasite effectors and verified its central role in initiating host cell cycle changes. Additionally, we report here the time-resolved kinetics of host cell cycle transition in response to HCE1/TEEGR, using the fluorescence ubiquitination cell cycle indicator reporter line (FUCCI), and reveal the existence of a block in S-phase progression and host DNA synthesis in several cell lines commonly used in the study of T. gondii. Importantly, we have observed that this S-phase block is not due to additional dense granule effectors but rather is dependent on the host cell line background and contact inhibition status of the host monolayer in vitro. This work highlights intriguing differences in the host response to reprogramming by the parasite and raises interesting questions regarding how parasite effectors differentially manipulate the host cell depending on the in vitro or in vivo context.

Original languageEnglish (US)
Pages (from-to)e0016022
JournalmSphere
Volume7
Issue number3
DOIs
StatePublished - Jun 29 2022

Keywords

  • FUCCI
  • HCE1
  • HCE1/TEEGR
  • S-phase
  • TEEGR
  • Toxoplasma gondii
  • cell cycle
  • cyclin E
  • host-parasite interaction
  • parasite effectors
  • Humans
  • DNA Replication
  • Protozoan Proteins/genetics
  • Contact Inhibition
  • DNA
  • Toxoplasma/physiology

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

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