NF-κB and MicroRNA Deregulation Mediated by HTLV-1 Tax and HBZ

Fochi, Stefania; Ciminale, Vincenzo; Trabetti, Elisabetta; Bertazzoni, Umberto; D’Agostino, Donna M.; Zipeto, Donato

doi:10.3390/pathogens8040290

Cited by 23 publications

(20 citation statements)

References 153 publications

(184 reference statements)

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“…Several studies have described a dysregulation of miRNA expression in HTLV-1-infected T cell lines, ATLL cell lines, and ATLL patient samples suggesting potential roles in ATLL pathogenesis [111,[223][224][225][226][227][228]. Tax interferes with the miRNA machinery by forming a complex with DROSHA to trigger its degradation through the proteasomal pathway, thus repressing its function and resulting in enhanced viral replication [229].…”

Section: Tax Modulation Of Mirna Expression For T Cell Proliferationmentioning

confidence: 99%

Mechanisms of Oncogenesis by HTLV-1 Tax

Mohanty

Harhaj

2020

Pathogens

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The human T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATLL), a neoplasm of CD4+CD25+ T cells that occurs in 2–5% of infected individuals after decades of asymptomatic latent infection. Multiple HTLV-1-encoded regulatory proteins, including Tax and HTLV-1 basic leucine zipper factor (HBZ), play key roles in viral persistence and latency. The HTLV-1 Tax oncoprotein interacts with a plethora of host cellular proteins to regulate viral gene expression and also promote the aberrant activation of signaling pathways such as NF-κB to drive clonal proliferation and survival of T cells bearing the HTLV-1 provirus. Tax undergoes various post-translational modifications such as phosphorylation and ubiquitination that regulate its function and subcellular localization. Tax shuttles in different subcellular compartments for the activation of anti-apoptotic genes and deregulates the cell cycle with the induction of DNA damage for the accumulation of genomic instability that can result in cellular immortalization and malignant transformation. However, Tax is highly immunogenic and therefore HTLV-1 has evolved numerous strategies to tightly regulate Tax expression while maintaining the pool of anti-apoptotic genes through HBZ. In this review, we summarize the key findings on the oncogenic mechanisms used by Tax that set the stage for the development of ATLL, and the strategies used by HTLV-1 to tightly regulate Tax expression for immune evasion and viral persistence.

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Section: Tax Modulation Of Mirna Expression For T Cell Proliferationmentioning

confidence: 99%

Mechanisms of Oncogenesis by HTLV-1 Tax

Mohanty

Harhaj

2020

Pathogens

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“…Each miRNA can target several mRNAs involved in different cell functions and in a crosstalk between cell signaling pathways. Deregulation of miRNA expression has been associated with several pathological processes, including cancer, neurodegenerative diseases, cardiovascular diseases, and host response to viral infections [30][31][32][33].…”

Section: Mirna Biogenesis and Functional Rolementioning

confidence: 99%

Regulation of microRNAs in Satellite Cell Renewal, Muscle Function, Sarcopenia and the Role of Exercise

Fochi

Giuriato

Simone

et al. 2020

IJMS

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Sarcopenia refers to a condition of progressive loss of skeletal muscle mass and function associated with a higher risk of falls and fractures in older adults. Musculoskeletal aging leads to reduced muscle mass and strength, affecting the quality of life in elderly people. In recent years, several studies contributed to improve the knowledge of the pathophysiological alterations that lead to skeletal muscle dysfunction; however, the molecular mechanisms underlying sarcopenia are still not fully understood. Muscle development and homeostasis require a fine gene expression modulation by mechanisms in which microRNAs (miRNAs) play a crucial role. miRNAs modulate key steps of skeletal myogenesis including satellite cells renewal, skeletal muscle plasticity, and regeneration. Here, we provide an overview of the general aspects of muscle regeneration and miRNAs role in skeletal mass homeostasis and plasticity with a special interest in their expression in sarcopenia and skeletal muscle adaptation to exercise in the elderly.

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“…Although the evidence of a potential effect of protease inhibitors in HTLV-1 infection is still limited, the hypothesized mechanism of action on NF-kB system activation encourage further detailed studies. Actually, one common and crucial feature of HTLV-1 infected/transformed cells is the up regulation of NF-kB very likely induced by transactivation of Tax protein [56]. Thus, the role of protease inhibitors in HTLV-1 infection could be targeting cellular determinants induced by infection rather than directly affecting the assembly of viral particles.…”

Section: Translational Approaches With Integrase and Protease Inhibitmentioning

confidence: 99%

Antiretroviral Therapy in HTLV-1 Infection: An Updated Overview

et al. 2020

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The human T cell leukemic/lymphotropic virus type 1 (HTLV-1), discovered several years ago, is the causative agent for a rapid progressive haematological malignancy, adult T cell leukemia (ATL), for debilitating neurological diseases and for a number of inflammatory based diseases. Although the heterogeneous features of the diseases caused by HTLV-1, a common topic concerning related therapeutic treatments relies on the use of antiretrovirals. This review will compare the different approaches and opinions in this matter, giving a concise overview of preclinical as well as clinical studies covering all the aspects of antiretrovirals in HTLV-1 infection. Studies will be grouped on the basis of the class of antiretroviral, putting together both pre-clinical and clinical results and generally following a chronological order. Analysis of the existing literature highlights that a number of preclinical studies clearly demonstrate that different classes of antiretrovirals, already utilized as anti-HIV agents, are actually capable to efficiently contrast HTLV-1 infection. Nevertheless, the results of most of the clinical studies are generally discouraging on the same point. In conclusion, the design of new antiretrovirals more specifically focused on HTLV-1 targets, and/or the establishment of early treatments with antiretrovirals could hopefully change the perspectives of diseases caused by HTLV-1.

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NF-κB and MicroRNA Deregulation Mediated by HTLV-1 Tax and HBZ

Cited by 23 publications

References 153 publications

Mechanisms of Oncogenesis by HTLV-1 Tax

Mechanisms of Oncogenesis by HTLV-1 Tax

Regulation of microRNAs in Satellite Cell Renewal, Muscle Function, Sarcopenia and the Role of Exercise

Antiretroviral Therapy in HTLV-1 Infection: An Updated Overview

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