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Cited by 20T-cell and Retrovirus StudiesViral-associated cancers and disordersHepatitis B Virus Studies

The DOI matches its Crossref record; 73 of the 73 references it cites were found in a registry or an index.

In vivo antagonistic role of the Human T-Cell Leukemia Virus Type 1 regulatory proteins Tax and HBZ

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Akkouche, Abdou, Moodad, Sara, Hleihel, Rita, Skayneh, Hala, Chambeyron, Séverine, El Hajj, Hiba, Bazarbachi, Ali·2021·PLOS Pathogens
DOI 10.1371/journal.ppat.1009219PMC PMC7817025
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Abstract

Adult T cell leukemia (ATL) is an aggressive malignancy secondary to chronic infection by the human T-cell leukemia virus type 1 (HTLV-1) infection. Two viral proteins, Tax and HBZ, play central roles in ATL leukemogenesis. Tax expression transforms T cells in vitro and induces ATL-like disease in mice. Tax also induces a rough eye phenotype and increases hemocyte count in Drosophila melanogaster, indicative of transformation. Among multiple functions, Tax modulates the expression of the enhancer of zeste homolog 2 (EZH2), a methyltransferase of the Polycomb Repressive Complex 2 (PRC2), leading to H3K27me3-dependent reprogramming of around half of cellular genes. HBZ is a negative regulator of Tax-mediated viral transcription. HBZ effects on epigenetic signatures are underexplored. Here, we established an hbz transgenic fly model, and demonstrated that, unlike Tax, which induces NF-κB activation and enhanced PRC2 activity creating an activation loop, HBZ neither induces transformation nor NF-κB activation in vivo. However, overexpression of Tax or HBZ increases the PRC2 activity and both proteins directly interact with PRC2 complex core components. Importantly, overexpression of HBZ in tax transgenic flies prevents Tax-induced NF-κB or PRC2 activation and totally rescues Tax-induced transformation and senescence. Our results establish the in vivo antagonistic effect of HBZ on Tax-induced transformation and cellular effects. This study helps understanding long-term HTLV-1 persistence and cellular transformation and opens perspectives for new therapeutic strategies targeting the epigenetic machinery in ATL.

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  • Tax modulates expression of NF-κB and enhancer Polycomb Repressive Complex 2 (PRC2), which governs persistence and cellular transformation.

    “Tax was shown to modulate the expression of NF-κB and the enhancer Polycomb Repressive Complex 2 (PRC2), which governs persistence and cellular transformation.”

    From Current State of Therapeutics for HTLV-1 (2024) · cites this paper as [157]

    The Results section reports that Tax activates NF-κB, enhances PRC2 activity, and induces transformation that depends on NF-κB and partly on PRC2. The Discussion links persistent infection to HBZ alleviating Tax’s deleterious effects; it does not show that Tax’s modulation of NF-κB and PRC2 governs persistence. No page numbers are available in our copy. (LLM, conf=0.84)

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  • Overexpression of Hbz prevents Tax-induced NF-κB and PRC2 activation.

    “Overexpression of Hbz was observed to prevent Tax-induced NF-κB and PRC2 activation, shedding light on the co-modulatory interplay of Tax and Hbz [157].”

    From Current State of Therapeutics for HTLV-1 (2024) · cites this paper as [157]

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Metadata

Authors
Akkouche, A., Moodad, S., Hleihel, R., Skayneh, H., Chambeyron, S., El Hajj, H., & Bazarbachi, A.
Affiliations
  • American University of Beirut (LB)
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
Bazarbachi, Ali
ORCID
Venue
PLOS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2021-01-20
Volume
17
Issue
1
Pages
e1009219
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1009219
PMC
PMC7817025
OpenAlex
W3124694565
Cited by
20
References
73
Citations by year
2026: 2 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 4
FWCI
1.49
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • American University of Beirut
  • Lady Tata Memorial Trust
  • National Institutes of Health (NIH P40OD018537, P40OD018537)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
  • Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
  • Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
Keywords
HTLV-1, taxation, HBZ, adult T-cell leukemia/lymphoma, cell transformation, polycomb repressive complex 2, EZH2, H3K27me3, NF-κB, epigenetic reprogramming, Drosophila melanogaster, senescence, viral transcription regulation
MeSH terms
Animals, Drosophila melanogaster, HeLa Cells, Humans, Retroviridae Proteins, Human T-lymphotropic virus 1, HTLV-I Infections, Gene Expression Regulation, Viral, Gene Products, tax, Cellular Senescence, Basic-Leucine Zipper Transcription Factors

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