Human T-Cell Leukemia Virus (HTLV) Infection and Treatment: 2nd Edition

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: 30 April 2026 | Viewed by 5771

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Guest Editor
Animal Models and Retroviral Vaccines Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
Interests: retrovirology; HTLV; animal models; immunology; molecular virology
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Guest Editor
1. Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
2. Global Virus Network Center of Excellence, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
Interests: immunology; viral infectious diseases; bacterial and parasitic infections; emerging infections; hepatitis; HIV
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We invite you to contribute original research and/or review to this Special Issue of Viruses that will highlight advances in HTLV-1 research.

The first human retrovirus human T-cell leukemia virus type 1 (HTLV-1) was identified in 1980. As a retrovirus, HTLV-1 integrates into the host genome and causes a persistent lifelong infection. Although the majority of infected individuals remain asymptomatic, a fraction of patients will progress to develop one of several severe diseases. HTLV-1 causes an aggressive fatal malignancy known as adult T-cell leukemia/lymphoma (ATLL), the neurodegenerative disease HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV-1 associated uveitis, infectious dermatitis and inflammatory conditions such as respiratory disease, Sjögren’s syndrome, rheumatoid arthritis, fibromyalgia and ulcerative colitis. In addition, HTLV-1 infection is associated with a higher mortality and morbidity. Thus far, no specific differences in viral strains have been identified to account for the differences in disease manifestation. Although a high viral DNA burden in peripheral blood mononuclear cells is a documented risk factor for ATLL and HAM/TSP, and HAM/TSP patients have a higher proviral load in cerebrospinal fluid than in peripheral blood, the virus level alone is not sufficient to differentiate symptomatic patients from healthy carriers, suggesting the importance of other factors, including the host immune response.

While many high-income countries have initiated HTLV-1 screening for blood donations, few other public health measures have been employed to prevent infection or manage/treat ATLL and HAM/TSP. Further, it is difficult to evaluate the public health burden because of the major gaps in the epidemiology of HTLV-1 infection. Even in areas of high prevalence, the awareness of HTLV-1 modes of transmission, disease course and strategies for clinical management are not readily available. Despite the profound impact HTLV-1 has on patient lives, minimal significant progress has been made in developing HTLV-1 vaccines or therapies for these diseases, with the prognosis for ATLL still being poor and HAM/TSP remaining an intractable disease.

Despite being investigated for over 40 years, many fundamental questions in HTLV-1 pathogenesis remain unresolved. In this Special Issue, we will focus on the most recent advances in understanding the mechanism of HTLV infection, with an emphasis on treatment and diagnosis. We will also focus on new developments in biomarkers, prevention, animal models and disease pathogenesis.

Dr. Cynthia A. Pise-Masison
Dr. Damian F. J. Purcell
Guest Editors

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Keywords

  • HTLV
  • HTLV-associated myelopathy/tropical spastic paraparesis
  • adult T-cell leukemia/lymphoma
  • inflammation
  • neurodegeneration
  • therapeutics
  • infectious dermatitis
  • cancer
  • antiviral drugs

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Related Special Issue

Published Papers (5 papers)

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Research

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17 pages, 2603 KB  
Article
Common Acquisition of Broadly Neutralizing Antibodies in an HTLV-1c+ First Nations Cohort from Central Australia
by Samantha L. Grimley, Sarah C. Monard, Ashley Hirons, Ashley H. Y. Yap, Sarah Collins, David Yurick, Georges Khoury, Paula C. Ellenberg, Marc Pellegrini, Lloyd J. Einsiedel and Damian F. J. Purcell
Viruses 2026, 18(4), 402; https://doi.org/10.3390/v18040402 - 24 Mar 2026
Viewed by 368
Abstract
Human T-cell leukemia virus type-1 (HTLV-1) is endemic to numerous regions worldwide, including Central Australia. The Australo-Melanesian subtype-C is endemic within Australia and Oceania, whereas subtype-A is the most widely distributed subtype globally. The lack of an approved vaccine highlights HTLV-1 as a [...] Read more.
Human T-cell leukemia virus type-1 (HTLV-1) is endemic to numerous regions worldwide, including Central Australia. The Australo-Melanesian subtype-C is endemic within Australia and Oceania, whereas subtype-A is the most widely distributed subtype globally. The lack of an approved vaccine highlights HTLV-1 as a neglected public health issue. To inform the development of HTLV-1 Envelope (Env)-based vaccines, we assessed anti-Env antibodies in an HTLV-1c+ cohort of First Nations individuals in Central Australia. Of the 62 plasma samples from patients with confirmed HTLV-1 serological diagnosis, 76% were positive for Env binding in ELISA, but 90% neutralized HTLV-1c pseudovirus (PSV) infection. Neutralization breadth with the capability of blocking both subtype-A and subtype-C PSV infection was identified in 100% of samples tested. Proviral load was positively associated with anti-Env response, with binding epitopes mapping to the proline-rich region of gp46-SU. Env-directed IgG showed the capacity to engage Fcγ receptors key to inducing antibody-dependent cellular cytotoxicity/phagocytosis responses. Serological response was not associated with comorbidities linked to HTLV-1c in this population (bronchiectasis, chronic kidney disease, diabetes). These findings demonstrate that potent humoral immunity arises and is sustained during HTLV-1 infection, suggesting that an Env-based vaccine displaying authentically native epitopes will be capable of recapitulating these neutralizing responses. Full article
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9 pages, 300 KB  
Communication
HIV/HTLV-1/2 Co-Infection in the Peruvian Amazon: Prevalence and Associated Factors
by Wieslawa-Guivanni Alava-Flores, Ivonne Navarro-del-Aguila, Silvia Otero-Rodriguez, José-Manuel Ramos-Rincón and Martin Casapia-Morales
Viruses 2026, 18(3), 338; https://doi.org/10.3390/v18030338 - 10 Mar 2026
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Abstract
Co-infection with human T-cell lymphotropic virus types 1 and 2 (HTLV-1/2) and HIV is not routinely screened for, yet it may significantly influence clinical progression, mortality, and quality of life in affected individuals. This study aimed to estimate the prevalence of HTLV-1/2 co-infection [...] Read more.
Co-infection with human T-cell lymphotropic virus types 1 and 2 (HTLV-1/2) and HIV is not routinely screened for, yet it may significantly influence clinical progression, mortality, and quality of life in affected individuals. This study aimed to estimate the prevalence of HTLV-1/2 co-infection among adults living with HIV and to identify associated epidemiological factors in the Peruvian Amazon. A cross-sectional study was conducted including patients receiving antiretroviral therapy through the multidisciplinary TARGA program in Iquitos, Peru, during the second quarter of 2013. Screening for HTLV-1/2 antibodies was performed using enzyme-linked immunosorbent assay, with reactive samples confirmed by Line Immunoassay. Demographic and behavioral variables were collected, and prevalence odds ratios with 95% confidence intervals were estimated using logistic regression models. Among the 284 patients included, 28 were co-infected with HIV and HTLV-1/2, resulting in a prevalence of 10% with a 95% confidence interval of 6.5 to 14.1. In multivariable analysis, age over 35 years and having more than 10 lifetime sexual partners were independently associated with co-infection, with prevalence odds ratios of 12.4 and 3.6, respectively. HTLV-1/2 co-infection was highly prevalent among people living with HIV in the Peruvian Amazon, and the main risk factors identified suggest that cumulative exposure and sexual behavior play a significant role in the joint transmission of both retroviruses, supporting the need to consider systematic HTLV screening in endemic settings. Full article
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Review

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13 pages, 796 KB  
Review
Targeting PRMT5 in Adult T-Cell Leukemia/Lymphoma: Opportunities and Challenges
by Kyle Ernzen and Amanda R. Panfil
Viruses 2026, 18(1), 94; https://doi.org/10.3390/v18010094 - 9 Jan 2026
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Abstract
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy caused by persistent infection with human T-cell leukemia virus type 1 (HTLV-1). ATLL remains difficult to treat despite intensive chemotherapy, antiviral therapy, and hematopoietic stem cell transplantation. The limited durability of current treatment strategies [...] Read more.
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy caused by persistent infection with human T-cell leukemia virus type 1 (HTLV-1). ATLL remains difficult to treat despite intensive chemotherapy, antiviral therapy, and hematopoietic stem cell transplantation. The limited durability of current treatment strategies highlights the need for mechanism-based therapeutic approaches. Protein arginine methyltransferase 5 (PRMT5) is a type II arginine methyltransferase that regulates transcription, RNA splicing, DNA damage responses, and immune signaling through symmetric dimethylation of histone and non-histone substrates. PRMT5 is frequently overexpressed across hematologic and solid tumors. Preclinical studies indicate that PRMT5 expression is elevated during HTLV-1-mediated T-cell transformation and that pharmacologic inhibition of PRMT5 selectively impairs the survival and transformation of infected T cells in vitro and in vivo. In this review, we highlight the current understanding of PRMT5 biology in cancer, summarize preclinical studies supporting PRMT5 as a therapeutic target in ATLL, and discuss key challenges to future clinical translation. We also discuss emerging approaches such as rational combination therapies and tumor-selective PRMT5 inhibitors as potential paths toward treatment for ATLL. Full article
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19 pages, 955 KB  
Review
HTLV-1 and ATLL: Epidemiology, Oncogenesis, and Opportunities for Community-Informed Research in the United States
by Adrian Altieri, Sean Patrick Reilly, Abu Mansalay, Alan Soo-Beng Khoo, Nettie Johnson, Zafar K. Khan, Amy Leader, Pooja Jain and Pierluigi Porcu
Viruses 2025, 17(10), 1333; https://doi.org/10.3390/v17101333 - 30 Sep 2025
Cited by 3 | Viewed by 2772
Abstract
Human T-cell leukemia virus type 1 (HTLV-1), the first oncogenic human retrovirus, causes adult T-cell leukemia/lymphoma (ATLL), an aggressive neoplasm of mature CD4+ T-cells that is incurable in most patients and is associated with a median survival of less than 1 year. HTLV-1 [...] Read more.
Human T-cell leukemia virus type 1 (HTLV-1), the first oncogenic human retrovirus, causes adult T-cell leukemia/lymphoma (ATLL), an aggressive neoplasm of mature CD4+ T-cells that is incurable in most patients and is associated with a median survival of less than 1 year. HTLV-1 also causes inflammatory disorders, including HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and uveitis. The estimated lifetime risks of ATLL and HAM/TSP in HTLV-1 carriers are 3–5% and 0.25–1.8%, respectively. Although there is uncertainty about other health effects of HTLV-1, a recent meta-analysis showed an association between HTLV-1 and cardiovascular, cerebrovascular, and metabolic diseases and a 57% increased risk of early mortality in HTLV-1 carriers, independent of ATLL or HAM/TSP. Furthermore, emerging studies in endemic areas show that outcomes for common cancers, such as cervical cancer and lymphoma (non-ATLL), are inferior in HTLV-1 carriers compared to publicly reported data. Thus, the impact of HTLV-1 may be greater and more diverse than currently understood. This review provides an outline of the prevalence and impact of HTLV-1 and associated disorders in the US, focused on—but not limited to—ATLL, with an emphasis on the social determinants of health that can affect the success of screening and prevention strategies. We also discuss the mechanisms by which HTLV-1 drives the pathogenesis of ATLL and potential strategies for early diagnosis and intervention. Finally, we conclude by suggesting approaches to designing and implementing community-informed research initiatives in HTLV-1 and ATLL. Full article
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Other

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12 pages, 1470 KB  
Opinion
The Complexity of Bovine Leukemia Virus Oncogenesis
by Florine Doucet, Alexis Fontaine, Malik Hamaidia, Jean-Rock Jacques, Thomas Jouant, Nour Mhaidly, Songkang Qin, Roxane Terres, Xavier Saintmard, Luc Willems and Manon Zwaenepoel
Viruses 2025, 17(12), 1609; https://doi.org/10.3390/v17121609 - 12 Dec 2025
Cited by 2 | Viewed by 816
Abstract
Bovine leukemia virus (BLV) is a retrovirus infecting several bovid species, notably Bos taurus, where it fulfills Koch’s postulates for pathogenicity. The virus primarily targets B-lymphocytes, establishing lifelong infections that remain mostly asymptomatic but can progress to lymphocytosis or lymphoma. Transmission occurs [...] Read more.
Bovine leukemia virus (BLV) is a retrovirus infecting several bovid species, notably Bos taurus, where it fulfills Koch’s postulates for pathogenicity. The virus primarily targets B-lymphocytes, establishing lifelong infections that remain mostly asymptomatic but can progress to lymphocytosis or lymphoma. Transmission occurs through live infected cells via blood, milk, or transplacental routes. Despite a robust antiviral immunity, BLV replicates by producing virions (i.e., the infectious cycle) or inducing mitosis of infected cells (i.e., clonal expansion). The immune system effectively controls the infectious cycle but fails to impede clonal expansion, leading to chronic immune activation and immunosuppression. BLV modifies the transcriptome of the host cell by expressing oncogenic factors (Tax), viral microRNAs and antisense RNAs. Leukemogenesis arises from cumulative alterations of the virus (e.g., 5′-end deletions of the integrated provirus and histone modifications of the LTR promoter) and the host cell (e.g., genomic mutations and favorable chromatin integration). This model underscores a unique persistence strategy, linking chronic infection, immune evasion, and slow multistep oncogenesis in the bovine host. Full article
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