Article (Scientific journals)
The helicase-like transcription factor redirects the autophagic flux and restricts human T-cell leukemia virus type 1 infection
Beauvois, Aurélie; Gazon, Hélène; Chauhan, Pradeep Singh et al.
2023In Proceedings of the National Academy of Sciences of the United States of America, 120 (31), p. 2216127120
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Keywords :
HTLV-1; HLTF; restriction factors; intrinsic immunity; Tax
Abstract :
[en] Retroviruses and their host have co-evolved in a delicate balance between viral replication and survival of the infected cell. In this equilibrium, restriction factors expressed by infected cells control different steps of retroviral replication such as entry, uncoating, nuclear import, expression, or budding. Here, we describe a mechanism of restriction against human T-cell leukemia virus type 1 (HTLV-1) by the helicase-like transcription factor (HLTF). We show that RNA and protein levels of HLTF are reduced in primary T-cells of HTLV-1 infected subjects, suggesting a clinical relevance. We further demonstrate that the viral oncogene Tax represses HLTF transcription via the Enhancer of zeste homolog 2 (EZH2) methyltransferase of the Polycomb repressive complex 2 (PRC2). The Tax protein also directly interacts with HLTF and induces its proteasomal degradation. RNA interference and gene transduction in HTLV-1 infected T-cells derived from patients indicate that HLTF is a restriction factor. Restoring the normal levels of HLTF expression induces the dispersal of the Golgi apparatus and overproduction of secretory granules. By synergizing with Tax-mediated NF-B activation, physiologically-relevant levels of HLTF intensify the autophagic flux. Increased vesicular trafficking leads to an enlargement of the lysosomes and the production of large vacuoles containing viral particles. HLTF induction in HTLV-1 infected cells significantly increases the percentage of defective virions. In conclusion, HLTF-mediated activation of the autophagic flux blunts the infectious replication cycle of HTLV-1, revealing a new mode of viral restriction.
Research center :
GIGA-CME - GIGA Cancer-Cellular and Molecular Epigenetics - ULiège
Disciplines :
Oncology
Author, co-author :
Beauvois, Aurélie  ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Cellular and Molecular Epigenetics
Gazon, Hélène  ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Cellular and Molecular Epigenetics
Chauhan, Pradeep Singh ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Cellular and Molecular Epigenetics
Jamakhani, Majeed ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Cellular and Molecular Epigenetics
Jacques, Jean-Rock  ;  Université de Liège - ULiège > Département GxABT > Microbial technologies
Thiry, Marc  ;  Université de Liège - ULiège > Département des sciences de la vie > Service collectif des enseignements de biologie en bachelier
Dejardin, Emmanuel ;  Université de Liège - ULiège > GIGA > GIGA I3 - Molecular Immunology and Signal Transduction
Di Valentin, Emmanuel  ;  Université de Liège - ULiège > GIGA > GIGA Platform Viral vectors
Twizere, Jean-Claude  ;  Université de Liège - ULiège > GIGA > GIGA Molecular Biology of Diseases - Viral Interactomes Network
Péloponèse, Jean-Marie;  Institut de Recherche en Infectiologie de Montpellier
Njock, Makon-Sébastien  ;  Centre Hospitalier Universitaire de Liège - CHU > > Service de rhumatologie
Yasunaga, Jun-Ichirou;  Kumamoto University > Department of Hematology
Matsuoka, Masao;  Kumamoto University > Department of Hematology
Hamaïdia, Malik   ;  Université de Liège - ULiège > Département GxABT > Microbial technologies
Willems, Luc   ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Cellular and Molecular Epigenetics
More authors (5 more) Less
 These authors have contributed equally to this work.
Language :
English
Title :
The helicase-like transcription factor redirects the autophagic flux and restricts human T-cell leukemia virus type 1 infection
Publication date :
2023
Journal title :
Proceedings of the National Academy of Sciences of the United States of America
ISSN :
0027-8424
eISSN :
1091-6490
Publisher :
National Academy of Sciences, Washington, United States - District of Columbia
Volume :
120
Issue :
31
Pages :
e2216127120
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
Télévie [BE]
Belgian Foundation Against Cancer [BE]
Leon Fredericq Foundation [BE]
Funding number :
CDR J.0195.21; PDR T.0261.20
Funding text :
Télévie grants from the Belgian National Fund for Scientific Research; Commission permanente facultaire à la recherche; the Léon Fredericq Foundation. A.B.
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