New Insights into HTLV-1-Related Inflammatory Diseases

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: 31 January 2027 | Viewed by 1051

Special Issue Editors


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Guest Editor
Division of Neurology, Yohkoh Rehabilitation Hospital, Nagasaki, Japan
Interests: HTLV-1; HAM/TSP; immunology; virology; treatment; neurology

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Guest Editor
Division of Neuroimmunology, Joint Research Center for Human Retrovirus Infection, Kagoshima University, Kagoshima, Japan
Interests: HTLV-1; HAM/TSP; CTL; immunology; innate immunity; neurology

Special Issue Information

Dear Colleagues,

Human T-cell leukemia virus-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is induced by chronic inflammation in the spinal cord triggered by HTLV-1 infection. The discovery of HAM/TSP revealed that HTLV-1 has the potential to induce not only aggressive lymphoproliferation as the oncovirus leading to the development of adult T-cell leukemia (ATL), but also profound inflammatory status by immunologic activations. Indeed, there are many reports that several inflammatory diseases, such as uveitis, myositis, pulmonary disorder, arthritis, and Sjögren’s syndrome, occasionally occur in HTLV 1-infected individuals, including HAM/TSP patients. Thus, there has been an increasing awareness that HTLV-1 is a powerful inflammation causative agent. Looking into the diseases induced by HTLV-1 infection from the point of view of the inflammatory status, in this Special Issue, we aim to foster open and active discussion on the clinical and molecular characteristics, as well as therapeutic strategies, of HTLV-1-related inflammatory diseases, including HAM/TSP. We warmly invite colleagues to contribute original research articles or reviews to this Special Issue.

Dr. Tatsufumi Nakamura
Dr. Ryuji Kubota
Guest Editors

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Keywords

  • HTLV-1
  • inflammation
  • treatment
  • HAM/TSP
  • HTLV-1-related inflammatory status

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Published Papers (2 papers)

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Research

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12 pages, 1706 KB  
Article
Transferrin Receptor Marks a Foxp3-Low Treg-like Inflammatory T Cell Subset Associated with Disease Severity in HAM/TSP
by Shinsuke Nakajima, Masaki Hino, Norihiro Takenouchi, Yoshihisa Yamano, Makoto Yamagishi, Tokifumi Odaka, Fhahira Rizkhika Admadiani, Cecile Faye, Kaoru Uchimaru, Jun-Ichi Fujisawa and Kazu Okuma
Pathogens 2026, 15(4), 450; https://doi.org/10.3390/pathogens15040450 - 21 Apr 2026
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Abstract
Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease driven by HTLV-1-infected CD4+ T cells; however, the phenotypic and functional characteristics of disease-associated T-cell subsets remain incompletely understood. We analyzed samples using flow cytometry ( [...] Read more.
Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease driven by HTLV-1-infected CD4+ T cells; however, the phenotypic and functional characteristics of disease-associated T-cell subsets remain incompletely understood. We analyzed samples using flow cytometry (n = 3–5 per group) and RNA-seq (n = 13), focusing on CADM1highCD4+ T cells enriched for HTLV-1-infected cells to evaluate a transferrin receptor (TfR)-expressing subset. TfR+CADM1highCD4+ T cells were detected in both asymptomatic carriers and patients with HAM, but their frequency among CD4+ T cells was higher in HAM patients. These cells exhibited a Treg-like phenotype with higher Foxp3 and CTLA-4 expression than TfR cells and showed increased Ki-67 positivity, consistent with proliferation. Despite this phenotype, they produced interferon-γ, indicating inflammatory potential, while Foxp3 expression was lower in HAM patients than in asymptomatic carriers, suggesting a more inflammatory phenotype. Furthermore, TfR transcript levels (RNA-seq TPM) correlated with clinical indicators of disease activity, including neopterin and CXCL10 protein levels, and the Osame motor disability score. Collectively, these findings suggest that TfR identifies a proliferative, Foxp3-low, Treg-like inflammatory CD4+ T-cell subset that is associated with disease activity in HAM. Full article
(This article belongs to the Special Issue New Insights into HTLV-1-Related Inflammatory Diseases)
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Review

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17 pages, 882 KB  
Review
Therapeutic Approaches for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis: Current and Emerging Strategies
by Tatsufumi Nakamura and Katsuya Satoh
Pathogens 2026, 15(5), 555; https://doi.org/10.3390/pathogens15050555 - 20 May 2026
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Abstract
Human T-cell leukemia virus-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease of the spinal cord induced by immunological activation due to high HTLV-1 proviral load in the peripheral blood. HAM/TSP is representative of HTLV-1-related inflammatory diseases, and its main neurological [...] Read more.
Human T-cell leukemia virus-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease of the spinal cord induced by immunological activation due to high HTLV-1 proviral load in the peripheral blood. HAM/TSP is representative of HTLV-1-related inflammatory diseases, and its main neurological symptoms—namely, motor dysfunction of the lower extremities through spastic paraparesis with urinary disturbance—are progressive and lead to deterioration in the quality of life of patients once these dysfunctions develop. Therefore, novel and safe therapeutic regimens are needed, enabling patients to commence treatment as soon as possible after the diagnosis of HAM/TSP. To date, various treatments have been developed for the correction of the associated immunological or virological abnormalities, which have produced some good results. However, there are still many problems, such as insufficient treatment effects and side effects. In addition, most of these treatments have only been characterized in the short term, being in the open trial phase, and it remains unclear whether or not they are suitable for the long-term treatment of HAM/TSP induced by a chronic inflammatory status. Thus, we need effective therapeutic regimens with safety for long-term or even lifelong courses of treatment. In this review, we summarize the clinical trials conducted to date for various therapeutic approaches, including representative regimens against HAM/TSP, while touching on the problematic issues. In addition, we discuss several agents with the potential to enable the development of novel therapeutic regimens as emerging interventions for further investigation in future research. Full article
(This article belongs to the Special Issue New Insights into HTLV-1-Related Inflammatory Diseases)
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