École Normale Supérieure de Lyon — France
Immunology and Microbiology · Life Sciences
19h-index821citations55works0.32yr avg
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Research Topics
T-cell and Retrovirus Studies(34), Animal Disease Management and Epidemiology(27), Vector-Borne Animal Diseases(26), Cytomegalovirus and herpesvirus research(4), interferon and immune responses(4)
Publications55 total
Over the recent years, there has been a renewed interest in the genetic variability of the human oncogenic retrovirus HTLV-1 (Human T-cell Leukemia Virus type 1), following reports of high prevalences of infection with HTLV-1 genotype c in remote aboriginal populations in Central Australia, and acknowledgment of the remarkably high genetic diversity of HTLV-1 in Central Africa. While clinical and epidemiological studies suggest that HTLV-1 genotypes might be associated with varying risks of pathological manifestations, molecular comparisons of the viral determinants among genotypes remain scarce. In this study, we provide the first comprehensive comparative analysis of the major oncoprotein Tax1 from genotypes a (Japanese), b (African) and c (Australo-Melanesia). Using unbiased analysis of image cytometry data from Tax1-expressing Jurkat T-cells, combined with proximity interactomics, we first show that Tax1 variants exhibit distinct subcellular localization in T-cells. Indeed, in contrast to Tax1a that assembles a NF-kB-activating signalosome at the surface of the Golgi apparatus, Tax1c lacks any significant association with this cell compartment. Surprisingly however, Tax1c does not show any general defect in NF-kB activation compared to Tax1a and Tax1b. Instead, transcriptomics analysis combined with pathway inference indicate that the quality of the NF-kB signature induced by Tax1c differs from that of Tax1a, and that the transcriptional landscape of Tax1c-expressing cells is biased towards T-cell activation and inflammation, an observation that is consistent with the kinome profiling of Tax1c-expressing cells. Analysis of Tax1b-induced transcriptional modulation revealed that it closely parallels that of Tax1a, but with an overall higher magnitude. In addition, distinct modulation of cell cycle-related kinase activity by Tax1b compared to Tax1a was correlated with a specific modulation of the cell cycle. Consistently, functional cell transformation assays demonstrated that Tax1b presents a higher oncogenic potential compared to Tax1a, while Tax1c harbours a decreased transforming activity. Altogether, we provide evidence of functional divergence among Tax1 from different genotypes that may have pathophysiological and clinical implications.
Open MIND·2026
Journal of Virology·2025· 1 citedOpen Access
PLoS Pathogens·2024· 1 citedOpen Access
Research Square (Research Square)·2024Open Access
Viruses·2022· 6 citedOpen Access
Life Science Alliance·2022· 7 citedOpen Access
Communications Biology·2021· 22 citedOpen Access
Pathogens·2021· 2 citedOpen Access
Virologie·2020
Frontiers in Microbiology·2020· 19 citedOpen Access
Scientific Reports·2019· 22 citedOpen Access
PLoS Pathogens·2019· 70 citedOpen Access
Virologie·2019· 1 citedOpen Access
Virologie·2019Open Access
Frontiers in Microbiology·2019· 31 citedOpen Access
PLoS neglected tropical diseases·2018· 20 citedOpen Access
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Frequent Co-authors
Renaud Mahieux(35), Hélène Dutartre(13), Sandrine Alais(10), Ali Bazarbachi(8), Jocelyn Turpin(7), Sébastien Alain Chevalier(6), Jennifer Vinera(5), Aurélien Schwob(5), Estelle Douceron(4), Nga Ling Ko(4), Antoine Gessain(4), Henri Gruffat(4), Andrea Cimarelli(4), Claudine Pique(4), Gergès Rizkallah(4), Élodie Teruel(4), Xuan-Nhi Nguyen(3), Youmna Kfoury(3), Amandine Bonnet(3), Arnaud Favre-Bonvin(3)