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Theileria parasites subvert E2F signaling to stimulate leukocyte proliferation.

ABSTRACT: Intracellular pathogens have evolved intricate mechanisms to subvert host cell signaling pathways and ensure their own propagation. A lineage of the protozoan parasite genus Theileria infects bovine leukocytes and induces their uncontrolled proliferation causing a leukemia-like disease. Given the importance of E2F transcription factors in mammalian cell cycle regulation, we investigated the role of E2F signaling in Theileria-induced host cell proliferation. Using comparative genomics and surface plasmon resonance, we identified parasite-derived peptides that have the sequence-specific ability to increase E2F signaling by binding E2F negative regulator Retinoblastoma-1 (RB). Using these peptides as a tool to probe host E2F signaling, we show that the disruption of RB complexes ex vivo leads to activation of E2F-driven transcription and increased leukocyte proliferation in an infection-dependent manner. This result is consistent with existing models and, together, they support a critical role of E2F signaling for Theileria-induced host cell proliferation, and its potential direct manipulation by one or more parasite proteins.

SUBMITTER: Tretina K

PROVIDER: S-EPMC7055300 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Theileria parasites subvert E2F signaling to stimulate leukocyte proliferation.

Tretina Kyle K Haidar Malak M Madsen-Bouterse Sally A SA Sakura Takaya T Mfarrej Sara S Fry Lindsay L Chaussepied Marie M Pain Arnab A Knowles Donald P DP Nene Vishvanath M VM Ginsberg Doron D Daubenberger Claudia A CA Bishop Richard P RP Langsley Gordon G Silva Joana C JC

Scientific reports 20200304 1

Intracellular pathogens have evolved intricate mechanisms to subvert host cell signaling pathways and ensure their own propagation. A lineage of the protozoan parasite genus Theileria infects bovine leukocytes and induces their uncontrolled proliferation causing a leukemia-like disease. Given the importance of E2F transcription factors in mammalian cell cycle regulation, we investigated the role of E2F signaling in Theileria-induced host cell proliferation. Using comparative genomics and surface ...[more]

PMID: 32132598

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Project description:BACKGROUND: Theileria and Babesia protozoan parasites are transmitted mainly by tick vectors. These parasites cause heavy economic losses to the live-stock industry, as well as affecting the health of wild animals in parasite-endemic areas. Identification of infectious agents in wild animals is not only crucial for species preservation, but also provides valuable information on parasite epidemiology. Here, we conducted a molecular surveillance study in Northwestern China to assess the prevalence of blood pathogens in cervids. METHODS: PCR analysis and microscopic evaluation of blood smears to detect Theileria- and Babesia-related diseases in Cervidae were conducted, in which 22 blood samples from red deer (n?=?22) in Qilian Mountain and 20 from sika deer (n?=?20) in Long Mountain were collected and tested for the presence of Theileria and Babesia. The 18S rRNA gene was amplified, and selected polymerase chain reaction (PCR)-positive samples were sequenced for species identification. RESULTS: PCR revealed that 9.1% of the Qilian Mountain samples and 20% of the Long Mountain samples were positive for Theileria uilenbergi; 90.09% of the Qilian Mountain samples (n?=?22) were positive for T. capreoli, but all of the Long Mountain samples (n?=?20) were negative for T. capreoli; no other Theileria or Babesia species were found. PCR showed that T. uilenbergi and T. capreoli were present in red deer in Qilian Mountain, while only T. uilenbergi was found in sika Deer in Long Mountain. The 18S rRNA gene sequences were aligned against the corresponding GenBank sequences of known isolates of Theileria and Babesia and subjected to phylogenetic analysis. The phylogenetic tree showed that the newly isolated Theileria spp. could be classified as belonging to two clades: one group belonged to the same clade as T. uilenbergi, the other to a clade containing T. capreoli. CONCLUSIONS: Our results provide important data to increase understanding of the epidemiology of Cervidae theileriosis, and will assist with the implementation of measures to control theileriosis transmission to Cervidae and small ruminants in central China.

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Theileria parasites subvert E2F signaling to stimulate leukocyte proliferation.

Publications

Theileria parasites subvert E2F signaling to stimulate leukocyte proliferation.

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