Human T-Cell Lymphotropic Virus Type 1 Transactivator Tax Exploits the XPB Subunit of TFIIH during Viral Transcription
| العنوان: | Human T-Cell Lymphotropic Virus Type 1 Transactivator Tax Exploits the XPB Subunit of TFIIH during Viral Transcription |
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| المؤلفون: | Florence Margottin-Goguet, Christophe Martella, Damien Groussaud, Claudine Pique, Bertha Cecilia Ramirez, Armelle Inge Tollenaere, Benoit Lacombe, Laetitia Waast |
| المساهمون: | Inserm U1016, Institut Cochin, Paris, France, 22 Rue Méchain, 75014 Paris, France, CNRS UMR8104, Paris, France, Université Paris Descartes, Sorbonne-Paris-Cité, Paris, France, Laboratoire de Recherche d'Hémobiologie Cochin, Hôpital Cochin, Paris, France. |
| المصدر: | J Virol Journal of Virology Journal of Virology, American Society for Microbiology, 2020, 94 (8), ⟨10.1128/JVI.02171-19⟩ |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | nucleotide excision-repair, Transcription, Genetic, [SDV]Life Sciences [q-bio], viruses, polymerase-ii transcription, RNA polymerase II, Virus Replication, Transactivation, 0302 clinical medicine, Human T cell lymphotropic virus type 1, Promoter Regions, Genetic, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Human T-lymphotropic virus 1, biology, General transcription factor, Gene Products, tax, tfiih, 3. Good health, Cell biology, Virus-Cell Interactions, retrovirus, oncoprotein, 030220 oncology & carcinogenesis, Transcription factor II H, Transcription factor II D, transcription, Transcription factor II A, Gene Expression Regulation, Viral, Immunology, mechanism, Microbiology, 03 medical and health sciences, Virology, nf-kappa-b, Humans, Transcription factor, 030304 developmental biology, promoter, htlv-1, Terminal Repeat Sequences, leukemia-lymphoma, gene-expression, HTLV-I Infections, HEK293 Cells, Insect Science, promoter opening, biology.protein, Trans-Activators, identification, activation, Transcription Factor TFIIH, Transcription Factors |
| الوصف: | Human T-cell lymphotropic virus type 1 (HTLV-1) Tax oncoprotein is required for viral gene expression. Tax transactivates the viral promoter by recruiting specific transcription factors but also by interfering with general transcription factors involved in the preinitiation step, such as TFIIA and TFIID. However, data are lacking regarding Tax interplay with TFIIH, which intervenes during the last step of preinitiation. We previously reported that XPB, the TFIIH subunit responsible for promoter opening and promoter escape, is required for Tat-induced human-immunodeficiency virus promoter transactivation. Here, we investigated whether XPB may also play a role in HTLV-1 transcription. We report that Tax and XPB directly interact in vitro and that endogenous XPB produced by HTLV-1-infected T cells binds to Tax and is recruited on proviral LTRs. In contrast, XPB recruitment at the LTR is not detected in Tax-negative HTLV-1-infected T cells and is strongly reduced when Tax-induced HTLV-1 LTR transactivation is blocked. XPB overexpression does not affect basal HTLV-1 promoter activation but enhances Tax-mediated transactivation in T cells. Conversely, downregulating XPB strongly reduces Tax-mediated transactivation. Importantly, spironolactone (SP)-mediated inhibition of LTR activation can be rescued by overexpressing XPB but not XPD, another TFIIH subunit. Furthermore, an XPB mutant defective for the ATPase activity responsible for promoter opening does not show rescue of the effect of SP. Finally, XPB downregulation reduces viability of Tax-positive but not Tax-negative HTLV-1-transformed T cell lines. These findings reveal that XPB is a novel cellular cofactor hijacked by Tax to facilitate HTLV-1 transcription. IMPORTANCE HTLV-1 is considered the most potent human oncovirus and is also responsible for severe inflammatory disorders. HTLV-1 transcription is undertaken by RNA polymerase II and is controlled by the viral oncoprotein Tax. Tax transactivates the viral promoter first via the recruitment of CREB and its cofactors to the long terminal repeat (LTR). However, how Tax controls subsequent steps of the transcription process remains unclear. In this study, we explore the link between Tax and the XPB subunit of TFIIH that governs, via its ATPase activity, the promoter-opening step of transcription. We demonstrate that XPB is a novel physical and functional partner of Tax, recruited on HTLV-1 LTR, and required for viral transcription. These findings extend the mechanism of Tax transactivation to the recruitment of TFIIH and reinforce the link between XPB and transactivator-induced viral transcription. |
| تدمد: | 1098-5514 0022-538X |
| DOI: | 10.1128/JVI.02171-19⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::128ed6c5fad7b84fddfbe1497ee2ff24 https://pubmed.ncbi.nlm.nih.gov/32024775 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....128ed6c5fad7b84fddfbe1497ee2ff24 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10985514 0022538X |
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| DOI: | 10.1128/JVI.02171-19⟩ |