Defining epitranscriptomic hallmarks at the host-parasite interface and their roles in virulence and disease progression in Theileria annulata-infected leukocytes

Malak Haidar; Tobias Mourier; Rahul Salunke; Abhinav Kaushik; Fathia Ben-Rached; Sara Mfarrej; Arnab Pain

doi:10.1016/j.bj.2025.100828

Defining epitranscriptomic hallmarks at the host-parasite interface and their roles in virulence and disease progression in Theileria annulata-infected leukocytes

Biomed J. 2025 Jan 9:100828. doi: 10.1016/j.bj.2025.100828. Online ahead of print.

Authors

Malak Haidar¹, Tobias Mourier², Rahul Salunke², Abhinav Kaushik², Fathia Ben-Rached², Sara Mfarrej², Arnab Pain³

Affiliations

¹ Pathogen Genomics Group, BESE Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Kingdom of Saudi Arabia; Biozentrum, University of Basel, 4056 Basel-Stadt, Switzerland. Electronic address: malak.haidar.1@kaust.edu.sa.
² Pathogen Genomics Group, BESE Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Kingdom of Saudi Arabia.
³ Pathogen Genomics Group, BESE Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Kingdom of Saudi Arabia; International Institute for Zoonosis Control, GI-CoRE, Hokkaido University, Sapporo, Japan. Electronic address: arnab.pain@kaust.edu.sa.

PMID: 39798869
DOI: 10.1016/j.bj.2025.100828

Abstract

Theileria parasites are known to induce the transformation of host bovine leukocytes, involved in rapid proliferation, evasion from apoptotic mechanisms, and increased dissemination. In this study, we reveal the involvement of m⁶A RNA modification in T. annulata infection-induced transformation of bovine leukocytes. We conducted m⁶A sequencing and bioinformatics analysis to map the mRNA methylation patterns of T. annulata-infected host leukocytes. We observe specific mRNA modifications for T. annulata-infected leukocytes and a strong correlation between the proliferation rate of the infected Leukocytes with m⁶A modifications We observe that the increased amounts of m⁶A seem to impact some cell cycle dynamics, potentially via modifications of E2F4 mRNA. Moreover, we further identify HIF-1α as a possible driver of these m⁶A RNA modifications that have clear relevance to cellular proliferation dynamics. Overall, our results provide insights into the role of m6A mRNA methylation in the molecular crosstalk between Theileria and their host leukocytes, emphasizing the critical role of mRNA methylation in host-parasite interaction.

Keywords: HIF1α; Theileria; m(6)A; proliferation.