Claudine Pique

Website: https://institutcochin.fr/equipes/retrovirus-infection-latence
ORCID: 0000-0001-8690-2440

HTLV-1 belongs to the small group of viruses associated to a cancer in human. Indeed, this retrovirus is responsible for Adult T-cell leukemia (ATL), a malignant proliferation of CD4+ T cells.

HTLV-1, alike all other retroviruses, is able to integrate its reverse-transcribed genome within the host cell genome, generating thereby the proviral genome flanked by two non-coding LTR regions (Long Terminal Repeats at both the 5’ and 3’ ends), containing transcriptional regulatory elements. The HTLV-1 genome encodes for structural proteins and enzymes as well as for regulatory and auxiliary proteins. Among the latter, two products have been shown to promote T-cell proliferation: the regulatory protein Tax (TransActivator of pX) and the auxiliary protein HBZ (HTLV-1 Basic Zipper protein).

During the last decade, we have discovered that Tax does not exist as a single species in the cell but rather as a myriad of sub-populations, each characterized by a particular combination of post-translational modifications. In particular, we demonstrated that Tax is ubiquitinated, notably via conjugation to non-degradative ubiquitin chain, and that this event is essential for the activation of the NF-kB pathway. We have also demonstrated that Tax is sumoylated and that these modified populations are present in the nucleus. We are now studying the role of post-translational modifications of Tax during the T cell transformation process.

More recently, we initiated new projects regarding the mechanisms by which HTLV-1 induces a transcriptional reprogramming of infected T lymphocytes. We studied in particular how the two HTLV-1 oncoproteins Tax and HBZ modulate DNA methylation and histone modifications and the link between these processes and the development of the different clinical forms of ATL.

Key words : retrovirus, NF-kB, PTM, transcription, epigenetic

Top 5 publications

1. Cheminant M, Lhermitte L, Bruneau J, Sicard H, Bonnafous C, Touzart A, Bourbon E, Ortonne N, Genestier L, Gaulard P, Palmic P, Suarez F, Frenzel L, Naveau L, Dussiot M, Waast L, Avettand Fenoel V, Brouzes C, Pique C, Lepelletier Y, Asnafi V, Marcais A, Hermine O.
KIR3DL2 contributes to the typing of acute-type adult T-cell leukemia and is a potential therapeutic target.
Blood. 2022 Jun 10:blood.2022016765. PMID: 35687761.

2. Martella C, Waast L, Pique C.
Tax, marionnettiste de la transcription du HTLV-1 [Tax, the puppet master of HTLV-1 transcription].
Med Sci (Paris). 2022 Apr;38(4):359-365. French. doi: 10.1051/medsci/2022039. PMID: 35485896.

3. Marçais A, Lhermitte L, Artesi M, Laurent C, Durkin K, Hahaut V, Rosewick N, Suarez F, Sibon D, Cheminant M, Avettand-Fenoel V, Bruneau J, Georges M, Pique C, Van den Broeke A, Asnafi V, Hermine O.
Targeted deep sequencing reveals clonal and subclonal mutational signatures in Adult T-cell leukemia/lymphoma and defines an unfavorable indolent subtype.
Leukemia. 2021 Mar;35(3):764-776. PMID: 32555298.

4. Martella C, Tollenaere AI, Waast L, Lacombe B, Groussaud D, Margottin-Goguet F, Ramirez BC, Pique C.
Human T-Cell Lymphotropic Virus Type 1 Transactivator Tax Exploits the XPB Subunit of TFIIH during Viral Transcription.
J Virol. 2020 Mar 31;94(8):e02171-19. PMID: 32024775.

5. Groussaud D, Khair M, Tollenaere AI, Waast L, Kuo MS, Mangeney M, Martella C, Fardini Y, Coste S, Souidi M, Benit L, Pique C*, Issad T*.
Hijacking of the O-GlcNAcZYME complex by the HTLV-1 Tax oncoprotein facilitates viral transcription.
PLoS Pathog. 2017 Jul 24;13(7):e1006518. PMID: 28742148.

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