Rigosertib is more potent than wortmannin and rapamycin against adult T‐cell leukemia‐lymphoma DOI
Mohsen Ghorbanzadeh Neghab, Mohammad Jalili‐Nik, Arash Soltani

et al.

BioFactors, Journal Year: 2023, Volume and Issue: 49(6), P. 1174 - 1188

Published: June 22, 2023

Human T lymphotropic virus type 1 (HTLV-1) infection can cause adult T-cell lymphoblastic leukemia (ATLL), an incurable, chemotherapy-resistant malignancy. In a quest for new therapeutic targets, our study sought to determine the levels of AKT, mTOR, and PI3K in ATLL MT-2 cells, HTLV-1 infected NIH/3T3 cells (Inf-3T3), patients (Carrier, HAM/TSP, ATLL). Furthermore, effects rigosertib, wortmannin, rapamycin on PI3K/Akt/mTOR pathway inhibit proliferation were examined. The results showed that mRNA expression Akt/PI3K/mTOR was down-regulated carrier, patients, as well MT-2, Inf-3T3 compared healthy individuals untreated controls. However, western blotting revealed increase phosphorylated activated forms AKT mTOR. Treating with rapamycin, rigosertib decreased Akt mTOR restored their levels. Using these inhibitors also significantly boosted pro-apoptotic genes, Bax/Bcl-2 ratio tumor suppressor gene p53 Inf-3T3cells. Rigosertib more potent than wortmannin inducing sub-G1 G2-M cell cycle arrest, late apoptosis cells. It synergized cytotoxic vincristine. These findings demonstrate downregulation level may occur negative feedback response increased PI3K-Akt-mTOR phosphorylation by HTLV-1. Therefore, using alone or combination common chemotherapy drugs be beneficial patients.

Language: Английский

Advances in preventive vaccine development against HTLV-1 infection: A systematic review of the last 35 years DOI Creative Commons
Carolina Souza Santana, Felipe de Oliveira Andrade, Greice Carolina Santos da Silva

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 13, 2023

Introduction The Human T-lymphotropic virus type 1 (HTLV-1) was the first described human retrovirus. It is currently estimated that around 5 to 10 million people worldwide are infected with this virus. Despite its high prevalence, there still no preventive vaccine against HTLV-1 infection. known development and large-scale immunization play an important role in global public health. To understand advances field we performed a systematic review regarding current progress of Methods This followed Preferred Reporting Items for Systematic Reviews Meta-analyses (PRISMA®) guidelines registered at International Prospective Register (PROSPERO). search articles PubMed, Lilacs, Embase SciELO databases. From 2,485 identified, 25 were selected according inclusion exclusion criteria. Results analysis these indicated potential designs available, although paucity studies clinical trial phase. Discussion Although discovered almost 40 years ago, it remains great challenge neglected threat. scarcity funding contributes decisively inconclusiveness development. data summarized here intends highlight necessity improve knowledge retrovirus, encouraging more on aiming eliminate registration https://www.crd.york.ac.uk/prospero , identifier (CRD42021270412).

Language: Английский

Citations

10
Animal Models Informing the Role of the Microbiome and its Metabolites in Rheumatoid Arthritis DOI
Jing Li, Jing He, Kristine A. Kuhn

et al.

Rheumatic Disease Clinics of North America, Journal Year: 2025, Volume and Issue: 51(2), P. 325 - 346

Published: Feb. 28, 2025

Language: Английский

Citations

0
Real-time monitoring of virus infection dynamics in established infection models for mechanism analysis DOI
Shu‐Jun Liu, Wenfeng Xu, Pengfei Jin

et al.

Chinese Chemical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 111076 - 111076

Published: March 1, 2025

Language: Английский

Citations

0
The critical role of ferroptosis in virus-associated hematologic malignancies and its potential value in antiviral-antitumor therapy DOI Creative Commons
Miao Miao, Yue‐Lei Chen, Xuehan Wang

et al.

Virulence, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 29, 2025

Epstein-Barr Virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and human T-cell leukemia virus type 1 (HTLV-1) are key infectious agents linked to the development of various hematological malignancies, including Hodgkin's lymphoma, non-Hodgkin's adult leukemia/lymphoma. This review highlights critical knowledge gaps in understanding role ferroptosis, a novel form cell death, virus-related tumors. We focus on how ferroptosis influences host response these viral infections, revealing groundbreaking mechanisms by which three viruses differentially regulate core pathways such as iron homeostasis, lipid peroxidation, antioxidant systems, thereby promoting malignant transformation cells. Additionally, we explore potential antiviral drugs modulators treatment virus-associated malignancies.

Language: Английский

Citations

0
Association Between IL-28B (rs8099917) and IL-28B (rs12979860) with Predisposition to Diseases Related to the HTLV-1: Systematic Review and Meta-Analysis DOI Creative Commons
Naomi Cuenca,

Damarys Cordero,

Brenda López-Ulloa

et al.

Pathogens, Journal Year: 2025, Volume and Issue: 14(5), P. 470 - 470

Published: May 13, 2025

This research addresses IL-28B gene polymorphisms (rs12979860 and rs8099917) to determine their association with HTLV-1-related diseases; it aims compare genotypic frequencies identify predisposition or protection, considering population, disease, controls. Given HTLV-1’s impact on immunity, this study seeks biomarkers for early diagnosis intervention. A systematic search met inclusion criteria, such as open access bibliographic experimental studies published in English between 2010 2024, genetic factors linked susceptibility pathologies. Regarding exclusion organisms other than humans, unofficial sources, non-indexed journals, scientific articles languages were ruled out. Statistical data analyses assessed using meta-analysis, including forest plot Q test of heterogeneity based the I2 statistics. The analyzed indicate associations genotypes, CT, GG, CC, TT rs12979890 rs8099917 various diseases, HCV, arthropathy, HAM/TSP, cytomegalovirus Crimean–Congo hemorrhagic fever associated HTLV-1; however, observed inconsistencies, high heterogeneity, deficiency related information limit consolidation findings. Further is needed clarify genotype interactions disease HTLV-1 infections.

Language: Английский

Citations

0
Oncoviruses (Human T-Cell Lymphotropic Viruses) and Lentiviruses (Human Immunodeficiency Virus Type 2) DOI

Michael A. Tolle,

Francesca Basile,

Susan L. Gillespie

et al.

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 1898 - 2016.e11

Published: Jan. 1, 2025

Language: Английский

Citations

0
Clinical and Mechanistic Implications of R-Loops in Human Leukemias DOI Open Access

Seo Yun Lee,

Kyle M. Miller, Jae‐Jin Kim

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5966 - 5966

Published: March 22, 2023

Genetic mutations or environmental agents are major contributors to leukemia and associated with genomic instability. R-loops three-stranded nucleic acid structures consisting of an RNA–DNA hybrid a non-template single-stranded DNA. These regulate various cellular processes, including transcription, replication, DSB repair. However, unregulated R-loop formation can cause DNA damage instability, which potential drivers cancer leukemia. In this review, we discuss the current understanding aberrant how it influences instability development. We also consider possibility as therapeutic targets for treatment.

Language: Английский

Citations

6
Role of miRNAs in Human T Cell Leukemia Virus Type 1 Induced T Cell Leukemia: A Literature Review and Bioinformatics Approach DOI Open Access
Caio Bezerra Machado,

Leidivan Sousa da Cunha,

Jersey Heitor da Silva Maués

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(10), P. 5486 - 5486

Published: May 14, 2022

Human T cell leukemia virus type 1 (HTLV-1) was identified as the first pathogenic human retrovirus and is estimated to infect 5 10 million individuals worldwide. Unlike other retroviruses, there no effective therapy prevent onset of most alarming diseases caused by HTLV-1, more severe cases manifest malignant phenotype adult (ATL). MicroRNA (miRNA) dysfunction a common feature leukemogenesis, it different in ATL cases. Therefore, we sought analyze studies that reported deregulated miRNA expression HTLV-1 infected cells patients’ samples understand how this deregulation could induce malignancy. Through silico analysis, 12 miRNAs stood out prediction targets, performed functional annotation genes linked these appeared have major biological interaction. A total 90 were enriched 14 KEGG pathways with significant values, including TP53, WNT, MAPK, TGF-β, Ras signaling pathways. These gene interactions are discussed further detail for elucidation they may act probable drivers onset, while our data provide solid starting points comprehension miRNAs’ roles infection, continuous effort oncologic research still needed improve understanding induced leukemia.

Language: Английский

Citations

9
Infection of the Ex Vivo Tonsil Model by HTLV-1 Envelope-Pseudotyped Viruses DOI Creative Commons
Mélanie Langlois, Salim Bounou, Michel J. Tremblay

et al.

Pathogens, Journal Year: 2023, Volume and Issue: 12(2), P. 182 - 182

Published: Jan. 24, 2023

Human T-cell leukemia virus type 1 (HTLV-1) is the causal agent of adult leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis. Its tropism known to be broad in cultured cell lines, while vivo data support a more selective transmission toward CD4+ T cells limited targeting other hematopoietic types. An essential condition for HTLV-1 infection cell-to-cell contact, which both virological synapse viral biofilm have been suggested strongly contribute. As lines animal models each present their own limitations studying replication, we explored use an ex model based on secondary lymphoid tonsillar tissue. HIV-1 luciferase-expressing pseudotyped viruses bearing envelope protein at surface were first shown recapitulate wide spectrum infectivity various lines. Tonsil fragments next exposed reproducibly infected. Infection by Env-pseudotyped was blocked different anti-gp46 antibodies, unlike virions. The dose-dependent revealed gradual increase luciferase activity, again sensitive antibodies. Overall, these results suggest that tonsil represents reliable alternative replication potentially latency, as well early clonal formation.

Language: Английский

Citations

4
Human T-cell leukemia virus type 1 is associated with dysthyroidism in the French Amazon DOI Creative Commons

Julia Dugardin,

Magalie Demar,

Nezha Hafsi

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: May 24, 2023

Background Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus known to cause two major diseases: adult leukemia/lymphoma and progressive neuromyelopathy—tropical spastic paraparesis. Many viruses may be involved in the pathogenesis of thyroiditis; however, few studies have focused on role HTLV-1. We aimed investigate association between HTLV-1 biological thyroid dysfunction. Methods included 357 patients with positive serology thyroid-stimulating hormone assay data 2012 2021 hospital French Guiana; we compared prevalence hypothyroidism hyperthyroidism this group that an HTLV-1-negative control (722 persons) matched for sex age. Results The infection was significantly higher than (11% versus 3.2% 11.3% 2.3%, respectively; p < 0.001). Conclusion Our study shows, first time, dysthyroidism large sample, suggesting function exploration should systematically implemented population as impact therapeutic management.

Language: Английский

Citations

4