Séminaire CIRI : Pr. Yorifumi SATOU

Pr. Yorifumi SATOU (Research Center for Human Retrovirus Infection, Kumamoto and Kagoshima Universities. – Japon): " Single cell analysis to elucidate mechanisms underlying oncogenesis caused by HTLV-1 "

Abstract: Human T-cell leukemia virus type 1 (HTLV-1) mainly infect CD4+ T-cells and induces chronic, persistent infection in infected individuals with some progressing to develop adult T-cell leukemia/lymphoma (ATL). HTLV-1 alters cellular differentiation, activation and survival but it is unknown if this contributes to malignant transformation. In this study, we used single-cell RNA-sequencing and TCR-sequencing to investigate T-cell differentiation and HTLV-1-mediated transformation processes. We analyzed 87,742 single cells from peripheral blood of 12 infected and 3 uninfected individuals. Trajectory analysis successfully captured physiological T-cell activation dynamics as well as ATL progression as a continuous process. Naive T-cells dynamically change into activated T-cells including infected cells, which seamlessly transitioned into ATL cells characterized by clonally expanded, highly-activated T-cells. In conclusion, our study revealed the mechanisms of HTLV-1-mediated transformation in vivo at single-cell level.