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Pharmaceuticals
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HTLV-1: Molecular Insights to Targeted Elimination Strategies
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HTLV-1: Molecular Insights to Targeted Elimination Strategies

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 30 November 2024 | Viewed by 4931

Special Issue Editors

Dr. Juliana Echevarria Neves de Lima

E-Mail Website
Guest Editor
Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil
Interests: HTLV-1; adult T-cell leukemia/Lymphoma (ATLL); HTLV-1-associated myelopathic/tropical spastic paraparesis (HAM/TSP); Immunology
Dr. Goedele N. Maertens

E-Mail Website
Guest Editor
Department of Infectious Disease, Imperial College London, London, UK
Interests: HTLV-1; integrase; integration; intasome assembly; PP2A-B56; integrase inhibitors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Estimates indicate that more than 10 million individuals live with human T-cell lymphotropic virus type 1 (HTLV-1) worldwide. HTLV-1 is a retrovirus responsible for highly aggressive neoplastic diseases, such as adult T-cell leukemia/Lymphoma (ATLL), and inflammatory diseases as HTLV-1-associated myelopathic/tropical spastic paraparesis (HAM/TSP). Despite the advances in understanding the pathogenesis of HTLV-1, there is still a need to develop more effective therapies. ATLL carriers have a poor prognosis for disease evolution and a low life expectancy. These patients usually receive combined chemotherapy, but the infected cells are resistant to a large part of the cell death-inducing agents. Moreover, asymptomatic people living with HTLV-1 or carriers of HTLV-1-related diseases are treated against some symptoms using corticosteroids. However, some new compounds or drug repositioning and immunotherapy have been described with treatment promising for HTLV-1-related disease. In addition, there is promise to use antiretrovirals as a pre-exposure prophylaxis. The aim of this Special Issue is to compilate the new findings in this area.

Dr. Juliana Echevarria Neves de Lima
Dr. Goedele N. Maertens
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • HTLV-1
  • adult T-cell leukemia/Lymphoma (ATLL)
  • HTLV-1-associated myelopathic/tropical spastic paraparesis (HAM/TSP)
  • treatment
  • new compounds
  • drug repositing and immunotherapy

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Published Papers (2 papers)

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Research

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16 pages, 2250 KiB  
Article
Cell Culture Evaluation Hints Widely Available HIV Drugs Are Primed for Success if Repurposed for HTLV-1 Prevention
by Mphatso D. Kalemera, Allison K. Maher, Margarita Dominguez-Villar and Goedele N. Maertens
Pharmaceuticals 2024, 17(6), 730; https://doi.org/10.3390/ph17060730 - 5 Jun 2024
Viewed by 1090
Abstract
With an estimated 10 million people infected, the deltaretrovirus human T-cell lymphotropic virus type 1 (HTLV-1) is the second most prevalent pathogenic retrovirus in humans after HIV-1. Like HIV-1, HTLV-1 overwhelmingly persists in a host via a reservoir of latently infected CD4+ [...] Read more.
With an estimated 10 million people infected, the deltaretrovirus human T-cell lymphotropic virus type 1 (HTLV-1) is the second most prevalent pathogenic retrovirus in humans after HIV-1. Like HIV-1, HTLV-1 overwhelmingly persists in a host via a reservoir of latently infected CD4+ T cells. Although most patients are asymptomatic, HTLV-1-associated pathologies are often debilitating and include adult T-cell leukaemia/lymphoma (ATLL), which presents in mature adulthood and is associated with poor prognosis with short overall survival despite treatment. Curiously, the strongest indicator for the development of ATLL is the acquisition of HTLV-1 through breastfeeding. There are no therapeutic or preventative regimens for HTLV-1. However, antiretrovirals (ARVs), which target the essential retrovirus enzymes, have been developed for and transformed HIV therapy. As the architectures of retroviral enzyme active sites are highly conserved, some HIV-specific compounds are active against HTLV-1. Here, we expand on our work, which showed that integrase strand transfer inhibitors (INSTIs) and some nucleoside reverse transcriptase inhibitors (NRTIs) block HTLV-1 transmission in cell culture. Specifically, we find that dolutegravir, the INSTI currently recommended as the basis of all new combination antiretroviral therapy prescriptions, and the latest prodrug formula of the NRTI tenofovir, tenofovir alafenamide, also potently inhibit HTLV-1 infection. Our results, if replicated in a clinical setting, could see transmission rates of HTLV-1 and future caseloads of HTLV-1-associated pathologies like ATLL dramatically cut via the simple repurposing of already widely available HIV pills in HTLV-1 endemic areas. Considering our findings with the old medical saying “it is better to prevent than cure”, we highly recommend the inclusion of INSTIs and tenofovir prodrugs in upcoming HTLV-1 clinical trials as potential prophylactics. Full article
(This article belongs to the Special Issue HTLV-1: Molecular Insights to Targeted Elimination Strategies)
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Review

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25 pages, 2728 KiB  
Review
New Perspectives about Drug Candidates Targeting HTLV-1 and Related Diseases
by Milena Cristina Martins da Silva, Renan Stefferson Barradas Pereira, Antonia Cherlly Aparecida Araujo, Ednilson Gregorio da Silva Filho, Anderson de Lima Dias, Kassio Silva Cavalcante and Maísa Silva de Sousa
Pharmaceuticals 2023, 16(11), 1546; https://doi.org/10.3390/ph16111546 - 2 Nov 2023
Cited by 2 | Viewed by 2918
Abstract
Among the human T-lymphotropic virus (HTLV) types, HTLV-1 is the most prevalent, and it has been linked to a spectrum of diseases, including HAM/TSP, ATLL, and hyperinfection syndrome or disseminated strongyloidiasis. There is currently no globally standard first-line treatment for HTLV-1 infection and [...] Read more.
Among the human T-lymphotropic virus (HTLV) types, HTLV-1 is the most prevalent, and it has been linked to a spectrum of diseases, including HAM/TSP, ATLL, and hyperinfection syndrome or disseminated strongyloidiasis. There is currently no globally standard first-line treatment for HTLV-1 infection and its related diseases. To address this, a comprehensive review was conducted, analyzing 30 recent papers from databases PubMed, CAPES journals, and the Virtual Health Library (VHL). The studies encompassed a wide range of therapeutic approaches, including antiretrovirals, immunomodulators, antineoplastics, amino acids, antiparasitics, and even natural products and plant extracts. Notably, the category with the highest number of articles was related to drugs for the treatment of ATLL. Studies employing mogamulizumab as a new perspective for ATLL received greater attention in the last 5 years, demonstrating efficacy, safe use in the elderly, significant antitumor activity, and increased survival time for refractory patients. Concerning HAM/TSP, despite corticosteroid being recommended, a more randomized clinical trial is needed to support treatment other than corticoids. The study also included a comprehensive review of the drugs used to treat disseminated strongyloidiasis in co-infection with HTLV-1, including their administration form, in order to emphasize gaps and facilitate the development of other studies aiming at better-directed methodologies. Additionally, docking molecules and computer simulations show promise in identifying novel therapeutic targets and repurposing existing drugs. These advances are crucial in developing more effective and targeted treatments against HTLV-1 and its related diseases. Full article
(This article belongs to the Special Issue HTLV-1: Molecular Insights to Targeted Elimination Strategies)
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