المؤلفون: Mohanty S; Department of Microbiology and Immunology, Penn State College School of Medicine, Hershey, PA, USA., Suklabaidya S; Department of Microbiology and Immunology, Penn State College School of Medicine, Hershey, PA, USA., Lavorgna A; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Millipore-Sigma, Rockville, MD, USA., Ueno T; Department of Microbiology, Kansai Medical University, Osaka, Japan., Fujisawa JI; Department of Microbiology, Kansai Medical University, Osaka, Japan., Ngouth N; Viral Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA., Jacobson S; Viral Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA., Harhaj EW; Department of Microbiology and Immunology, Penn State College School of Medicine, Hershey, PA, USA. ewh110@psu.edu.

المصدر: Nature communications [Nat Commun] 2024 Jun 25; Vol. 15 (1), pp. 5380. Date of Electronic Publication: 2024 Jun 25.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE

مواضيع طبية MeSH: Gene Products, tax*/metabolism , Gene Products, tax*/genetics , Human T-lymphotropic virus 1*/pathogenicity , Human T-lymphotropic virus 1*/genetics , Human T-lymphotropic virus 1*/physiology , Vascular Endothelial Growth Factor Receptor-2*/metabolism , Vascular Endothelial Growth Factor Receptor-2*/genetics , NF-kappa B*/metabolism , Paraparesis, Tropical Spastic*/virology , Paraparesis, Tropical Spastic*/metabolism , Cell Survival*, Humans ; Apoptosis ; HTLV-I Infections/virology ; HTLV-I Infections/metabolism ; CD4-Positive T-Lymphocytes/virology ; CD4-Positive T-Lymphocytes/metabolism ; T-Lymphocytes/metabolism ; T-Lymphocytes/virology ; Leukemia-Lymphoma, Adult T-Cell/virology ; Leukemia-Lymphoma, Adult T-Cell/metabolism ; Leukemia-Lymphoma, Adult T-Cell/genetics ; Leukemia-Lymphoma, Adult T-Cell/pathology ; Phosphorylation ; HEK293 Cells

مستخلص: Human T-cell leukemia virus type 1 (HTLV-1) infection is linked to the development of adult T-cell leukemia/lymphoma (ATLL) and the neuroinflammatory disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 Tax oncoprotein regulates viral gene expression and persistently activates NF-κB to maintain the viability of HTLV-1-infected T cells. Here, we utilize a kinome-wide shRNA screen to identify the tyrosine kinase KDR as an essential survival factor of HTLV-1-transformed cells. Inhibition of KDR specifically induces apoptosis of Tax expressing HTLV-1-transformed cell lines and CD4 + T cells from HAM/TSP patients. Furthermore, inhibition of KDR triggers the autophagic degradation of Tax resulting in impaired NF-κB activation and diminished viral transmission in co-culture assays. Tax induces the expression of KDR, forms a complex with KDR, and is phosphorylated by KDR. These findings suggest that Tax stability is dependent on KDR activity which could be exploited as a strategy to target Tax in HTLV-1-associated diseases.
(© 2024. The Author(s).)

المؤلفون: Hayati RF; Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, Japan., Nakajima R; Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, Japan., Zhou Y; Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, Japan., Shirasawa M; Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, Japan., Zhao L; Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, Japan., Fikriyanti M; Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, Japan., Iwanaga R; Department of Obstetrics and Gynecology, University of Colorado School of Medicine, 12700 East 19th Avenue, Aurora, CO 80045, USA., Bradford AP; Department of Obstetrics and Gynecology, University of Colorado School of Medicine, 12700 East 19th Avenue, Aurora, CO 80045, USA., Kurayoshi K; Division of Molecular Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Ishikawa, Japan., Araki K; Department of Morphological Biology, Ohu University School of Dentistry, 31-1 Misumido Tomitamachi, Koriyama 963-8611, Fukushima, Japan., Ohtani K; Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, Japan.

المصدر: Genes [Genes (Basel)] 2024 May 27; Vol. 15 (6). Date of Electronic Publication: 2024 May 27.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101551097 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4425 (Electronic) Linking ISSN: 20734425 NLM ISO Abbreviation: Genes (Basel) Subsets: MEDLINE

مواضيع طبية MeSH: Protein-Arginine N-Methyltransferases*/genetics , Protein-Arginine N-Methyltransferases*/metabolism , Gene Products, tax*/genetics , Gene Products, tax*/metabolism , Human T-lymphotropic virus 1*/genetics, Humans ; Cyclin D2/genetics ; Cyclin D2/metabolism ; Transcriptional Activation ; Interleukin-2 Receptor alpha Subunit/genetics ; Interleukin-2 Receptor alpha Subunit/metabolism ; NF-kappa B/metabolism ; NF-kappa B/genetics ; Histones/metabolism ; Histones/genetics ; Epigenesis, Genetic ; Jurkat Cells

مستخلص: Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma. The oncogene product Tax of HTLV-I is thought to play crucial roles in leukemogenesis by promoting proliferation of the virus-infected cells through activation of growth-promoting genes. These genes code for growth factors and their receptors, cytokines, cell adhesion molecules, growth signal transducers, transcription factors and cell cycle regulators. We show here that Tax activates the gene coding for coactivator-associated arginine methyltransferase 1 (CARM1), which epigenetically enhances gene expression through methylation of histones. Tax activated the Carm1 gene and increased protein expression, not only in human T-cell lines but also in normal peripheral blood lymphocytes (PHA-PBLs). Tax increased R17-methylated histone H3 on the target gene IL-2Rα , concomitant with increased expression of CARM1. Short hairpin RNA (shRNA)-mediated knockdown of CARM1 decreased Tax-mediated induction of IL-2Rα and Cyclin D2 gene expression, reduced E2F activation and inhibited cell cycle progression. Tax acted via response elements in intron 1 of the Carm1 gene, through the NF-κB pathway. These results suggest that Tax-mediated activation of the Carm1 gene contributes to leukemogenic target-gene expression and cell cycle progression, identifying the first epigenetic target gene for Tax-mediated trans-activation in cell growth promotion.

المؤلفون: Song X; Department of Microbiology and Molecular Genetics, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America., Qu Z; Department of Microbiology and Molecular Genetics, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America.; Department of Molecular Microbiology and Immunology, Hastings Center for Pulmonary Research, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA, United States of America.

المصدر: PloS one [PLoS One] 2024 May 09; Vol. 19 (5), pp. e0303138. Date of Electronic Publication: 2024 May 09 (Print Publication: 2024).

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural

بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

مواضيع طبية MeSH: Gene Products, tax*/metabolism , Gene Products, tax*/genetics , Human T-lymphotropic virus 1*/genetics , Human T-lymphotropic virus 1*/pathogenicity , Macrophages*/metabolism , Macrophages*/virology, Animals ; Humans ; Mice ; Adrenal Gland Neoplasms/virology ; Adrenal Gland Neoplasms/pathology ; Adrenal Gland Neoplasms/genetics ; Adrenal Gland Neoplasms/metabolism ; Mice, Transgenic ; NF-kappa B p50 Subunit/metabolism ; NF-kappa B p50 Subunit/genetics ; Terminal Repeat Sequences/genetics

مستخلص: Human T-cell leukemia virus type I (HTLV-I) is an oncogenic virus whose infection can cause diverse diseases, most notably adult T-cell leukemia/lymphoma (ATL or ATLL), an aggressive and fatal malignancy of CD4 T cells. The oncogenic ability of HTLV-I is mostly attributed to the viral transcriptional transactivator Tax. Tax alone is sufficient to induce specific tumors in mice depending on the promotor used to drive Tax expression, thereby being used to understand HTLV-I tumorigenesis and model the tumor types developed in Tax transgenic mice. Tax exerts its oncogenic role predominantly by activating the cellular transcription factor NF-κB. Here, we report that genetic deletion of NF-κB1, the prototypic member of the NF-κB family, promotes adrenal medullary tumors but suppresses neurofibromas in mice with transgenic Tax driven by the HTLV-I Long Terminal Repeat (LTR) promoter. The adrenal tumors are derived from macrophages. Neoplastic macrophages also infiltrate the spleen and lymph nodes, causing splenomegaly and lymphadenopathy in mice. Nevertheless, the findings could be human relevant, because macrophages are important target cells of HTLV-I infection and serve as a virus reservoir in vivo. Moreover, the spleen, lymph nodes and adrenal glands are the most common sites of tumor cell infiltration in HTLV-I-infected patients. These data provide new mechanistic insights into the complex interaction between Tax and NF-κB, therefore improving our understanding of HTLV-I oncogenic pathogenesis. They also expand our knowledge and establish a new animal model of macrophage neoplasms and adrenal tumors.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Song, Qu. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

المؤلفون: Su R; Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.; Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, China., Kang X; Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.; Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, China., Niu Y; Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.; Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, China., Zhao T; Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.; Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang, China., Wang H; Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, China.; Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Medical Technology, Xinxiang Medical University, Xinxiang, China.

المصدر: Frontiers in immunology [Front Immunol] 2024 Apr 16; Vol. 15, pp. 1375168. Date of Electronic Publication: 2024 Apr 16 (Print Publication: 2024).

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE

مواضيع طبية MeSH: Gene Products, tax*/metabolism , NF-kappa B*/metabolism , Human T-lymphotropic virus 1*/physiology , RNA-Binding Proteins*/metabolism , RNA-Binding Proteins*/genetics , DNA-Binding Proteins*/metabolism , DNA-Binding Proteins*/genetics , Heterogeneous-Nuclear Ribonucleoproteins*/metabolism , Heterogeneous-Nuclear Ribonucleoproteins*/genetics, Humans ; Signal Transduction ; HEK293 Cells ; Protein Binding ; Cell Proliferation ; HTLV-I Infections/metabolism ; HTLV-I Infections/virology ; Apoptosis ; I-kappa B Kinase/metabolism ; Host-Pathogen Interactions

مستخلص: Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma. The HTLV-1 Tax constitutively activates nuclear factor-κB (NF-κB) to promote the survival and transformation of HTLV-1-infected T cells. Despite extensive study of Tax, how Tax interacts with host factors to regulate NF-κB activation and HTLV-1-driven cell proliferation is not entirely clear. Here, we showed that overexpression of Poly (rC)-binding protein 1 (PCBP1) promoted Tax-mediated IκB kinase (IKK)-NF-κB signaling activation, whereas knockdown of PCBP1 attenuated Tax-dependent IKK-NF-κB activation. However, Tax activation of HTLV-1 long terminal repeat was unaffected by PCBP1. Furthermore, depletion of PCBP1 led to apoptosis and reduced proliferation of HTLV-1-transformed cells. Mechanistically, PCBP1 interacted and co-localized with Tax in the cytoplasm, and PCBP1 KH3 domain was indispensable for the interaction between PCBP1 and Tax. Moreover, PCBP1 facilitated the assembly of Tax/IKK complex. Collectively, our results demonstrated that PCBP1 may exert an essential effect in Tax/IKK complex combination and subsequent NF-κB activation, which provides a novel insight into the pathogenetic mechanisms of HTLV-1.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Su, Kang, Niu, Zhao and Wang.)

المؤلفون: Fadaee A; Faculty of Medicine, Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Azadi-Square, Medical Campus, Mashhad 9177948564, Iran; HTLV-1 Foundation, Ghaem Hospital, Mashhad University of Medical Sciences, Ahmad Abad Bolv., Mashhad, Iran., Mohammadi FS; Faculty of Medicine, Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Azadi-Square, Medical Campus, Mashhad 9177948564, Iran., Ariaee N; Faculty of Medicine, Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Azadi-Square, Medical Campus, Mashhad 9177948564, Iran., Ahmadi Ghezeldasht S; Blood Borne Infections Research Center, Academic Center for Education, Culture, and Research (ACECR), Razavi Khorasan, Mashhad, Iran., Valizadeh N; Faculty of Medicine, Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Azadi-Square, Medical Campus, Mashhad 9177948564, Iran., Kheradmand F; Immunology Research Center, Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran., Boostani R; HTLV-1 Foundation, Ghaem Hospital, Mashhad University of Medical Sciences, Ahmad Abad Bolv., Mashhad, Iran., Rafatpanah H; Faculty of Medicine, Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Azadi-Square, Medical Campus, Mashhad 9177948564, Iran; HTLV-1 Foundation, Ghaem Hospital, Mashhad University of Medical Sciences, Ahmad Abad Bolv., Mashhad, Iran., Rezaee SA; Faculty of Medicine, Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Azadi-Square, Medical Campus, Mashhad 9177948564, Iran; HTLV-1 Foundation, Ghaem Hospital, Mashhad University of Medical Sciences, Ahmad Abad Bolv., Mashhad, Iran. Electronic address: RezaeeR@mums.ac.ir.

المصدر: Multiple sclerosis and related disorders [Mult Scler Relat Disord] 2024 Jul; Vol. 87, pp. 105659. Date of Electronic Publication: 2024 Apr 29.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Elsevier B. V Country of Publication: Netherlands NLM ID: 101580247 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-0356 (Electronic) Linking ISSN: 22110348 NLM ISO Abbreviation: Mult Scler Relat Disord Subsets: MEDLINE

مواضيع طبية MeSH: Receptor, Cannabinoid, CB1*/metabolism , Receptor, Cannabinoid, CB2*/metabolism , Paraparesis, Tropical Spastic* , Human T-lymphotropic virus 1*, Humans ; Male ; Female ; Adult ; Middle Aged ; Gene Products, tax/metabolism ; Basic-Leucine Zipper Transcription Factors/metabolism ; Viral Load ; Retroviridae Proteins/metabolism

مستخلص: Background/aim: The roles of endocannabinoids are described in immune modulation and neuroprotection. HTLV-1-associated myelopathy (HAM/TSP) is an inflammatory neurodegenerative disease. Therefore, in this study, the interactions of HTLV-1 regulatory factors and host cannabinoid receptors (CBRs) were evaluated in HAM/TSP.
Methods: Nineteen HAM/TSPs, 22 asymptomatic carriers (ACs), and 18 healthy controls (HCs) were enrolled. RNA was extracted from PBMCs and then reverse-transcribed to cDNA. The gene expression of CB1R and CB2R, as well as HTLV-1 proviral load (PVL), Tax and HTLV-1 basic leucine zipper factor (HBZ) were assessed by RT-qPCR.
Results: The mean expression of CB1R in ACs (8.51 ± 2.76) was significantly higher than HAMTSPs (1.593 ± 0.74, p = 0.05) and also HCs (0.10 ± 0.039, p = 0.001). The CB2R gene expression level in ACs (2.62±0.44) was significantly higher than HAM/TSPs (0.59 ± 0.15, p = 0.001) and HCs (1.00 ± 0.2, p = 0.006). Meanwhile there was a strong correlation between CB1R and CB2R gene expression levels in the HCs and HAM/TSPs (p = 0.001). HTLV-1-Tax expression in HAM/TSPs (386 ± 104) was higher than ACs (75 ± 32) and statistically significant (p = 0.003). While HTLV-1-HBZ was only expressed in three AC subjects and five HAM/TSPs, thus it cannot be analyzed.
Conclusion: The up-regulation of CB2R has immunomodulatory effects in inflammatory reactions. While CB1R as a neuroprotective agent may suppress inflammatory reactions in ACs, preventing HAM/TSP. It seems that, like multiple sclerosis (MS), cannabinoid medications are beneficial in HAM/TSP.
Competing Interests: Declaration of competing interest All authors declare no potential conflict of interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)

المؤلفون: Fajami Z; Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran., Akbarin MM; Inflammation and Inflammatory Diseases Research Centre, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran., Rafatpanah H; Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran., Ramezani S; Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran., Rahimi H; Department of Hematology, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran., Rezaee SA; Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

المصدر: AIDS research and human retroviruses [AIDS Res Hum Retroviruses] 2024 Mar; Vol. 40 (3), pp. 141-147. Date of Electronic Publication: 2023 Sep 25.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Mary Ann Liebert Country of Publication: United States NLM ID: 8709376 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1931-8405 (Electronic) Linking ISSN: 08892229 NLM ISO Abbreviation: AIDS Res Hum Retroviruses Subsets: MEDLINE

مواضيع طبية MeSH: Leukemia-Lymphoma, Adult T-Cell*/genetics , Human T-lymphotropic virus 1*/genetics , HIV Infections*/pathology , Lymphoma*/pathology, Adult ; Humans ; Leukocytes, Mononuclear ; Basic-Leucine Zipper Transcription Factors/genetics ; Basic-Leucine Zipper Transcription Factors/metabolism ; Retroviridae Proteins/genetics ; Retroviridae Proteins/metabolism ; Gene Expression ; Gene Products, tax/genetics ; Gene Products, tax/metabolism

مستخلص: Adult T cell leukemia/lymphoma is a malignancy with a poor prognosis caused by human T lymphocyte virus type 1 (HTLV-1) infection. Tax and HBZ are two major viral proteins that may be involved in oncogenesis by disrupting apoptosis. Because Bcl-xL plays an integral role in the anti-apoptotic pathway, this study examines the interaction between host apoptosis and oncoproteins. We investigated 37 HTLV-1-infected individuals, including 18 asymptomatic and 19 adult T cell leukemia/lymphoma (ATLL) subjects. mRNA was extracted and converted to cDNA from peripheral blood mononuclear cells, and then gene expression was determined using TaqMan q-PCR. Moreover, the HTLV-1 proviral load (PVL) was also measured using a commercial absolute quantification kit (Novin Gene, Iran). Data analysis revealed that the mean of TAX , HBZ , and PVL was significantly higher among the study groups (ATLL and carrier groups p  = .003, p  = .000, and p  = .002 respectively). There was no statistical difference in Bcl-xL gene expression between the study groups ( p  = .323). It is proposed that this anti-apoptotic pathway may not be directly involved in the development of ATLL lymphoma. Bcl-xL , TAX, HBZ gene expression, and PVL can be utilized as prognostic markers.

المؤلفون: Marie P; Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210, Laboratory of Biology and Modelling of the Cell, 46 Allée d'Italie Site Jacques Monod, F-69007 Lyon, France., Bazire M; Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210, Laboratory of Biology and Modelling of the Cell, 46 Allée d'Italie Site Jacques Monod, F-69007 Lyon, France., Ladet J; Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210, Laboratory of Biology and Modelling of the Cell, 46 Allée d'Italie Site Jacques Monod, F-69007 Lyon, France., Ameur LB; Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210, Laboratory of Biology and Modelling of the Cell, 46 Allée d'Italie Site Jacques Monod, F-69007 Lyon, France., Chahar S; Institute of Genetics and Molecular and Cellular Biology (IGBMC), UMR7104, Centre National de la Recherche Scientifique, U1258, Institut National de la Santé et de la Recherche Médicale, University of Strasbourg, 6704 Illkirch, France., Fontrodona N; Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210, Laboratory of Biology and Modelling of the Cell, 46 Allée d'Italie Site Jacques Monod, F-69007 Lyon, France., Sexton T; Institute of Genetics and Molecular and Cellular Biology (IGBMC), UMR7104, Centre National de la Recherche Scientifique, U1258, Institut National de la Santé et de la Recherche Médicale, University of Strasbourg, 6704 Illkirch, France., Auboeuf D; Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210, Laboratory of Biology and Modelling of the Cell, 46 Allée d'Italie Site Jacques Monod, F-69007 Lyon, France., Bourgeois CF; Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210, Laboratory of Biology and Modelling of the Cell, 46 Allée d'Italie Site Jacques Monod, F-69007 Lyon, France., Mortreux F; Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210, Laboratory of Biology and Modelling of the Cell, 46 Allée d'Italie Site Jacques Monod, F-69007 Lyon, France.

المصدر: Nucleic acids research [Nucleic Acids Res] 2024 Feb 28; Vol. 52 (4), pp. 1527-1543.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE

مواضيع طبية MeSH: Chromatin Assembly and Disassembly*/genetics , NF-kappa B p50 Subunit*/metabolism , Gene Expression Regulation*, Alternative Splicing/genetics ; Gene Products, tax/genetics ; Gene Products, tax/metabolism ; Human T-lymphotropic virus 1/genetics ; Human T-lymphotropic virus 1/metabolism ; NF-kappa B/genetics ; NF-kappa B/metabolism ; Signal Transduction ; Transcription Factor RelA/genetics ; Transcription Factor RelA/metabolism ; Transcriptional Activation ; Humans

مستخلص: The NF-κB protein p65/RelA plays a pivotal role in coordinating gene expression in response to diverse stimuli, including viral infections. At the chromatin level, p65/RelA regulates gene transcription and alternative splicing through promoter enrichment and genomic exon occupancy, respectively. The intricate ways in which p65/RelA simultaneously governs these functions across various genes remain to be fully elucidated. In this study, we employed the HTLV-1 Tax oncoprotein, a potent activator of NF-κB, to investigate its influence on the three-dimensional organization of the genome, a key factor in gene regulation. We discovered that Tax restructures the 3D genomic landscape, bringing together genes based on their regulation and splicing patterns. Notably, we found that the Tax-induced gene-gene contact between the two master genes NFKBIA and RELA is associated with their respective changes in gene expression and alternative splicing. Through dCas9-mediated approaches, we demonstrated that NFKBIA-RELA interaction is required for alternative splicing regulation and is caused by an intragenic enrichment of p65/RelA on RELA. Our findings shed light on new regulatory mechanisms upon HTLV-1 Tax and underscore the integral role of p65/RelA in coordinated regulation of NF-κB-responsive genes at both transcriptional and splicing levels in the context of the 3D genome.
(© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

المؤلفون: Sudo H; Laboratory of Biochemistry, Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Shonan University of Medical Sciences, Kanagawa 244-0806, Japan., Tonoyama Y; Support Center for Student Practical Lab, Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Shonan University of Medical Sciences, Kanagawa 244-0806, Japan., Ikebe E; Research Center for Biological Products in the Next Generation, National Institute of Infectious Diseases, Tokyo 162-8640, Japan., Hasegawa H; Department of Laboratory Medicine, Nagasaki University Hospital, Nagasaki 852-8501, Japan., Iha H; Department of Microbiology, Faculty of Medicine, Oita University, Oita 879-5593, Japan; Division of Pathophysiology, The Research Center for GLOBAL and LOCAL Infectious Diseases (RCGLID), Faculty of Medicine, Oita University, Oita, Japan., Ishida YI; Laboratory of Biochemistry, Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Shonan University of Medical Sciences, Kanagawa 244-0806, Japan; Laboratory of Molecular and Cellular Biochemistry, Meiji Pharmaceutical University, Tokyo 204-8588, Japan. Electronic address: youichi.ishida@sums.ac.jp.

المصدر: Leukemia research [Leuk Res] 2024 Mar; Vol. 138, pp. 107454. Date of Electronic Publication: 2024 Feb 12.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Pergamon Press Country of Publication: England NLM ID: 7706787 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-5835 (Electronic) Linking ISSN: 01452126 NLM ISO Abbreviation: Leuk Res Subsets: MEDLINE

مواضيع طبية MeSH: Leukemia-Lymphoma, Adult T-Cell* , Human T-lymphotropic virus 1*/metabolism , Lymphoma*, Adult ; Humans ; Proteomics ; Biomarkers ; Digestion ; Gene Products, tax/metabolism ; Golgi Matrix Proteins

مستخلص: Adult T-cell leukemia/lymphoma (ATL), caused by human T-cell leukemia virus type-1 (HTLV-1) infection, is a malignant hematologic cancer that remains difficult to cure. We herein established a biomarker identification strategy based on the total cell proteomics of cultured ATL cells to search for novel ATL biomarkers. Four protocols with a combination of selected conditions based on lysis buffers and addition agents for total cell proteomics were used for a differential analysis between the ATL cell group (consisting of 11 cell lines), HTLV-1-infected cell group (consisting of 6 cell lines), and HTLV-1-negative cell group (consisting of 6 cell lines). In the analysis, we identified 24 and 27 proteins that were significantly increased (ratio ≥2.0, p < 0.05) and decreased (ratio ≤ 0.5, p < 0.05), respectively, in the ATL group. Previously reported CCL3 and CD30/TNFRSF8 were confirmed to be among significantly increased proteins. Furthermore, correlation analysis between identified proteins and Tax suggested that RASSF2 and GORASP2 were candidates of novel Tax-regulated factors. The biomarker identification strategy established herein is expected to contribute to the identification of biomarkers for ATL and other diseases.
Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)

المؤلفون: Beauvois A; Laboratory of Molecular and Cellular Epigenetics, Grappe Interdisciplinaire de Génoprotéomique Appliquée, University of Liège, 4000, Liège, Belgium.; Molecular Biology, Teaching and Research Center, University of Liège, 5030, Gembloux, Belgium., Gazon H; Laboratory of Molecular and Cellular Epigenetics, Grappe Interdisciplinaire de Génoprotéomique Appliquée, University of Liège, 4000, Liège, Belgium.; Molecular Biology, Teaching and Research Center, University of Liège, 5030, Gembloux, Belgium., Chauhan PS; Laboratory of Molecular and Cellular Epigenetics, Grappe Interdisciplinaire de Génoprotéomique Appliquée, University of Liège, 4000, Liège, Belgium.; Molecular Biology, Teaching and Research Center, University of Liège, 5030, Gembloux, Belgium., Jamakhani M; Laboratory of Molecular and Cellular Epigenetics, Grappe Interdisciplinaire de Génoprotéomique Appliquée, University of Liège, 4000, Liège, Belgium.; Molecular Biology, Teaching and Research Center, University of Liège, 5030, Gembloux, Belgium., Jacques JR; Laboratory of Molecular and Cellular Epigenetics, Grappe Interdisciplinaire de Génoprotéomique Appliquée, University of Liège, 4000, Liège, Belgium.; Molecular Biology, Teaching and Research Center, University of Liège, 5030, Gembloux, Belgium., Thiry M; Laboratory of Cell and Tissue Biology, Grappe Interdisciplinaire de Génoprotéomique Appliquée, University of Liège, 4000, Liège, Belgium., Dejardin E; Laboratory of Molecular Immunology & Signal Transduction, Grappe Interdisciplinaire de Génoprotéomique Appliquée, University of Liège, 4000, Liège, Belgium., Valentin ED; Viral Vectors Platform, Grappe Interdisciplinaire de Génoprotéomique Appliquée, University of Liège, 4000 Liège, Belgium., Twizere JC; Laboratory of Viral Interactomes, Unit of Molecular Biology of Diseases, Grappe Interdisciplinaire de Génoprotéomique Appliquée, University of Liège, 4000 Liège, Belgium., Péloponèse JM; Institut de Recherche en Infectiologie de Montpellier, Université de Montpellier, CNRS, 34094, Montpellier, France., Njock MS; Laboratory of Pneumology, Grappe Interdisciplinaire de Génoprotéomique Appliquée, University of Liège, University Hospital of Liège, 4000 Liège, Belgium., Yasunaga JI; Department of Hematology, Kumamoto University, 860-8556, Kumamoto, Japan., Matsuoka M; Department of Hematology, Kumamoto University, 860-8556, Kumamoto, Japan., Hamaïdia M; Laboratory of Molecular and Cellular Epigenetics, Grappe Interdisciplinaire de Génoprotéomique Appliquée, University of Liège, 4000, Liège, Belgium.; Molecular Biology, Teaching and Research Center, University of Liège, 5030, Gembloux, Belgium., Willems L; Laboratory of Molecular and Cellular Epigenetics, Grappe Interdisciplinaire de Génoprotéomique Appliquée, University of Liège, 4000, Liège, Belgium.; Molecular Biology, Teaching and Research Center, University of Liège, 5030, Gembloux, Belgium.

المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2023 Aug; Vol. 120 (31), pp. e2216127120. Date of Electronic Publication: 2023 Jul 24.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE

مواضيع طبية MeSH: Human T-lymphotropic virus 1*/metabolism , Leukemia, T-Cell*, Humans ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Gene Products, tax/genetics ; Gene Products, tax/metabolism ; T-Lymphocytes/metabolism ; NF-kappa B/metabolism ; DNA-Binding Proteins

مستخلص: Retroviruses and their host have coevolved 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 methyltransferase of the Polycomb repressive complex 2. 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-κB 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 an original mode of viral restriction.

المؤلفون: Caterino-de-Araujo A; Centro de Imunologia, Instituto Adolfo Lutz, São Paulo, SP, Brazil. Electronic address: adele.caterino@ial.sp.gov.br., Campos KR; Laboratório Estratégico, Centro de Respostas Rápidas, Instituto Adolfo Lutz, São Paulo, SP, Brazil.

المصدر: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases [Infect Genet Evol] 2021 Dec; Vol. 96, pp. 105141. Date of Electronic Publication: 2021 Nov 12.

نوع المنشور: Letter

بيانات الدورية: Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 101084138 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1567-7257 (Electronic) Linking ISSN: 15671348 NLM ISO Abbreviation: Infect Genet Evol Subsets: MEDLINE

مواضيع طبية MeSH: Gene Products, tax/*genetics , HTLV-I Infections/*diagnosis , Human T-lymphotropic virus 1/*isolation & purification, Gene Products, tax/isolation & purification ; Human T-lymphotropic virus 1/genetics ; Human T-lymphotropic virus 2 ; Humans ; Virion