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Cloned HTLV-1+CD4+, but not CD8+, T-cells display an oncogenic miRNome

Abstract : HTLV-1 persistence in vivo relies on the persistent clonal expansion of its host cells. These are CD4+ and CD8+ T cells, yet ATL is regularly CD4+. Accordingly, untransformed HTLV-1+CD4+ but not CD8+ T cells cloned from carriers cumulate the features of preleukemic cells, including multinuclearity, chromatin bridges, increased cell cycling and inappropriate telomerase activity. MicroRNAs (miR) modify the maturation of a plethora of T-cells RNA and their deregulation would therefore constitute an appropriate explanation for the Tax-dependent or -independent pleiotropic changes in the phenotype of HTLV-1+CD4+ T cells. As the miRNome of naturally infected untransformed cells has not been investigated to date, we assessed the miR expression profiling of T cells cloned from carriers. Microarray results, confirmed by quantitative RTPCR, showed that, upon infection, CD4+ and CD8+ clones yielded aberrant expression of 15 distinct miRs including miR-34b and miR-494 that were respectively over- and underexpressed in both compartments. The more prominent effect of the infection consisted in the CD4+-restricted overexpression of the cancer-related miRs miR-21, -27b and -23b associated with the CD4+-restricted downregulation of the proapoptotic miR-15 and -16. Data were extended by the analysis of 40 additional CD4+ clones (20 infected). Crossing the miRNome against the whole transcriptome data identified putative miR-targeted genes. In silico, those targeted by miR-23b and -27b defined 2 hitherto unknown pathways involving the cell cycle and genetic disorders. Therefore HTLV-1 triggers a phenotype-specific miR signature consistent with the preleukemic HTLV-1+CD4+ phenotyp
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https://hal-univ-lyon1.archives-ouvertes.fr/hal-02540445
Contributor : Depot 1 Lyon 1 <>
Submitted on : Saturday, April 11, 2020 - 9:09:10 AM
Last modification on : Friday, May 29, 2020 - 3:32:01 AM

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C. Vernin, C. Pinatel, N. Nazaret, E. Wattel, Catherine Legras-Lachuer, et al.. Cloned HTLV-1+CD4+, but not CD8+, T-cells display an oncogenic miRNome. Retrovirology, BioMed Central, 2011, 8 (Suppl 1), pp.A169. ⟨10.1186/1742-4690-8-S1-A169⟩. ⟨hal-02540445⟩

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