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Viruses
Special Issues
Human T-Cell Leukemia Virus (HTLV) Infection and Treatment
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Human T-Cell Leukemia Virus (HTLV) Infection and Treatment

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

Deadline for manuscript submissions: 31 May 2025 | Viewed by 7940

Special Issue Editors

Dr. Cynthia A. Pise-Masison

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Guest Editor
Animal Models and Retroviral Vaccines Section, Center for Cancer Research, National Cancer Institute, Bethesda, MA, USA
Interests: retrovirology; HTLV; animal models; immunology; molecular virology
Dr. Damian F.J. Purcell

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Guest Editor
1. Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
2. Global Virus Network Center of Excellence at 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 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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Viruses 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 2600 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
  • HTLV-associated myelopathy/tropical spastic paraparesis
  • adult T-cell leukemia/lymphoma
  • inflammation
  • neurodegeneration
  • therapeutics
  • infectious dermatitis
  • cancer
  • antiviral drugs

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Published Papers (5 papers)

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Research

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22 pages, 2994 KiB  
Article
HTLV-1 p13 Protein Hijacks Macrophage Polarization and Promotes T-Cell Recruitment
by Ramona Moles, Maria Omsland, Cynthia A. Pise-Masison, Jeffrey J. Subleski, Daniel W. McVicar, Sarkis Sarkis, Anna Gutowska, Luca Schifanella, Melvin Doster, Robyn Washington-Parks, Vincenzo Ciminale and Genoveffa Franchini
Viruses 2025, 17(4), 471; https://doi.org/10.3390/v17040471 - 26 Mar 2025
Viewed by 938
Abstract
The human T-cell leukemia type-1 (HTLV-1) retrovirus establishes chronic life-long infection in a fraction of infected individuals associated with severe pathological conditions. Although the mechanism driving disease development is not fully understood, current evidence indicates the essential functions of viral regulatory proteins. Among [...] Read more.
The human T-cell leukemia type-1 (HTLV-1) retrovirus establishes chronic life-long infection in a fraction of infected individuals associated with severe pathological conditions. Although the mechanism driving disease development is not fully understood, current evidence indicates the essential functions of viral regulatory proteins. Among these, the p13 protein has previously been shown to localize to the inner mitochondrial membrane in T cells, altering mitochondrial biology and T-cell function. While CD4+ T cells are the primary cell target of HTLV-1 infection, genomic viral DNA has also been detected in monocytes, macrophages, and dendritic cells, which orchestrate innate and adaptive immunity and play a critical role in protecting against virus-induce diseases by establishing the appropriate balance of pro and anti-inflammatory responses. Given the central role of mitochondria in monocyte differentiation, we investigated the effect of p13 in monocytes/macrophages and found that by localizing to mitochondria, p13 affects mitochondrial respiration. Moreover, we demonstrate that p13 expression affects macrophage polarization to favor the recruitment of CD4+ T cells, the primary target of the virus, potentially facilitating the spread of viral infection and the development of disease. Full article
(This article belongs to the Special Issue Human T-Cell Leukemia Virus (HTLV) Infection and Treatment)
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12 pages, 756 KiB  
Article
HTLV-1 Infection and Cervicovaginal Susceptibility to High-Risk HPV: Findings from Women Living with HTLV-1 in Salvador, Brazil
by Alisson de Aquino Firmino, Paulo Roberto Tavares Gomes Filho, Juliana Domett Siqueira, Luana Leandro Gois, Giselle Calasans de Souza Costa, Adenilda Lima Lopes Martins, Mariana Lima Drumond, Marcelo Alves Soares, Bernardo Galvão-Castro, Carlos Gustavo Régis da Silva and Maria Fernanda Rios Grassi
Viruses 2025, 17(2), 140; https://doi.org/10.3390/v17020140 - 22 Jan 2025
Viewed by 1558
Abstract
Persistent oncogenic HPV infection is strongly associated with cervical cancer. Studies have suggested a higher prevalence of HPV in women living with HTLV-1. This study aimed to determine whether HTLV-1 infection is associated with cervicovaginal HPV infection and to characterize HPV types according [...] Read more.
Persistent oncogenic HPV infection is strongly associated with cervical cancer. Studies have suggested a higher prevalence of HPV in women living with HTLV-1. This study aimed to determine whether HTLV-1 infection is associated with cervicovaginal HPV infection and to characterize HPV types according to oncogenic risk. Vaginal fluid samples were subjected to HPV diagnosis via PCR, and positive samples were subjected to Sanger sequencing and massive sequencing. Papanicolaou smears were examined using light microscopy to identify cell abnormalities. Among the 155 women screened, 79 were HTLV-1-infected and 76 were uninfected. HPV PCR identified 23 positive samples (15/79 vs. 8/76; p = 0.13). Twenty-three HPV types were identified, of which only types 31, 54, and 58 were present in both groups. When the number of HPV58 infections in each group was compared, women with HTLV-1 had a higher prevalence (8/79 versus 1/76; p = 0.03). In total, 61.9% of HTLV-1-infected women had at least one high-risk or probable high-risk HPV type (p = 0.12). Cytopathological findings were not significantly different between the groups. Further research is needed to determine whether HTLV-1 infection affects HPV progression and cervical cancer development and to assess the potential benefits of vaccination for women living with HTLV-1. Full article
(This article belongs to the Special Issue Human T-Cell Leukemia Virus (HTLV) Infection and Treatment)
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18 pages, 5236 KiB  
Article
Dendritic Cells Pulsed with HAM/TSP Exosomes Sensitize CD4 T Cells to Enhance HTLV-1 Infection, Induce Helper T-Cell Polarization, and Decrease Cytotoxic T-Cell Response
by Julie Joseph, Thomas A. Premeaux, Ritesh Tandon, Edward L. Murphy, Roberta Bruhn, Christophe Nicot, Bobby Brooke Herrera, Alexander Lemenze, Reem Alatrash, Prince Baffour Tonto, Lishomwa C. Ndhlovu and Pooja Jain
Viruses 2024, 16(9), 1443; https://doi.org/10.3390/v16091443 - 10 Sep 2024
Cited by 2 | Viewed by 1702
Abstract
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive demyelinating disease of the spinal cord due to chronic inflammation. Hallmarks of disease pathology include dysfunctional anti-viral responses and the infiltration of HTLV-1-infected CD4+ T cells and HTLV-1-specific CD8+ T cells in the central nervous [...] Read more.
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive demyelinating disease of the spinal cord due to chronic inflammation. Hallmarks of disease pathology include dysfunctional anti-viral responses and the infiltration of HTLV-1-infected CD4+ T cells and HTLV-1-specific CD8+ T cells in the central nervous system. HAM/TSP individuals exhibit CD4+ and CD8+ T cells with elevated co-expression of multiple inhibitory immune checkpoint proteins (ICPs), but ICP blockade strategies can only partially restore CD8+ T-cell effector function. Exosomes, small extracellular vesicles, can enhance the spread of viral infections and blunt anti-viral responses. Here, we evaluated the impact of exosomes isolated from HTLV-1-infected cells and HAM/TSP patient sera on dendritic cell (DC) and T-cell phenotypes and function. We observed that exosomes derived from HTLV-infected cell lines (OSP2) elicit proinflammatory cytokine responses in DCs, promote helper CD4+ T-cell polarization, and suppress CD8+ T-cell effector function. Furthermore, exosomes from individuals with HAM/TSP stimulate CD4+ T-cell polarization, marked by increased Th1 and regulatory T-cell differentiation. We conclude that exosomes in the setting of HAM/TSP are detrimental to DC and T-cell function and may contribute to the progression of pathology with HTLV-1 infection. Full article
(This article belongs to the Special Issue Human T-Cell Leukemia Virus (HTLV) Infection and Treatment)
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Review

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21 pages, 400 KiB  
Review
Dynamic Roles of RNA and RNA Epigenetics in HTLV-1 Biology
by Emily M. King and Amanda R. Panfil
Viruses 2025, 17(1), 124; https://doi.org/10.3390/v17010124 - 17 Jan 2025
Viewed by 1752
Abstract
Since the discovery of RNA in the early 1900s, scientific understanding of RNA form and function has evolved beyond protein coding. Viruses, particularly retroviruses like human T-cell leukemia virus type 1 (HTLV-1), rely heavily on RNA and RNA post-transcriptional modifications to regulate the [...] Read more.
Since the discovery of RNA in the early 1900s, scientific understanding of RNA form and function has evolved beyond protein coding. Viruses, particularly retroviruses like human T-cell leukemia virus type 1 (HTLV-1), rely heavily on RNA and RNA post-transcriptional modifications to regulate the viral lifecycle, pathogenesis, and evasion of host immune responses. With the emergence of new sequencing technologies in the last decade, our ability to dissect the intricacies of RNA has flourished. The ability to study RNA epigenetic modifications and splice variants has become more feasible with the recent development of third-generation sequencing technologies, such as Oxford nanopore sequencing. This review will highlight the dynamic roles of known RNA and post-transcriptional RNA epigenetic modifications within HTLV-1 biology, including viral hbz, long noncoding RNAs, microRNAs (miRNAs), transfer RNAs (tRNAs), R-loops, N6-methyladenosine (m6A) modifications, and RNA-based therapeutics and vaccines. Full article
(This article belongs to the Special Issue Human T-Cell Leukemia Virus (HTLV) Infection and Treatment)

Other

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9 pages, 1483 KiB  
Brief Report
Evaluation of QuantiFERON-TB Gold for the Diagnosis of Mycobacterium tuberculosis Infection in HTLV-1-Infected Patients
by Luana Leandro Gois, Natália Barbosa Carvalho, Fred Luciano Neves Santos, Carlos Gustavo Regis-Silva, Thainá Gonçalves Tolentino Figueiredo, Bernardo Galvão-Castro, Edgar Marcelino Carvalho and Maria Fernanda Rios Grassi
Viruses 2024, 16(12), 1873; https://doi.org/10.3390/v16121873 - 30 Nov 2024
Viewed by 1297
Abstract
Human T-cell leukemia virus type 1 (HTLV-1) is associated with an increased risk of tuberculosis (TB). This study aimed to evaluate the performance of the QuantiFERON-TB Gold (QFT) test for the diagnosis of Mycobacterium tuberculosis (MTB) infection in HTLV-1-infected individuals. HTLV-1-infected participants were [...] Read more.
Human T-cell leukemia virus type 1 (HTLV-1) is associated with an increased risk of tuberculosis (TB). This study aimed to evaluate the performance of the QuantiFERON-TB Gold (QFT) test for the diagnosis of Mycobacterium tuberculosis (MTB) infection in HTLV-1-infected individuals. HTLV-1-infected participants were divided into four groups: HTLV-1-infected individuals with a history of tuberculosis (HTLV/TB), individuals with positive HTLV and tuberculin skin tests (HTLV/TST+) or negative TST (HTLV/TST−), and HTLV-1-negative individuals with positive TST results (HN/TST+). We compared the diagnostic performance of the QFT assay with that of the TST as a reference and evaluated test sensitivity, specificity, accuracy, likelihood ratio, and diagnostic odds ratio. The results showed a higher frequency of positive TST results and induration diameter ≥10 mm in HTLV-1-infected individuals than in the controls. The QFT test was more frequently positive in the HTLV/TB group than in the other groups, while a combined analysis of HTLV/TB and HTLV/TST+ indicated a QFT sensitivity of 57.5%. No significant differences were found in the other diagnostic performance measures, as QFT test results were in agreement with TST results, particularly in TST-negative individuals. Given the low sensitivity of QFT for LTBI in individuals infected with HTLV-1, the TST may be preferable in regions where both infections are endemic. Full article
(This article belongs to the Special Issue Human T-Cell Leukemia Virus (HTLV) Infection and Treatment)
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