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Review

Human T-Lymphotropic Virus (HTLV): Epidemiology, Genetic, Pathogenesis, and Future Challenges

by
Francesco Branda
1,*,
Chiara Romano
1,
Grazia Pavia
2,
Viola Bilotta
1,
Chiara Locci
3,4,
Ilenia Azzena
4,
Ilaria Deplano
3,
Noemi Pascale
3,4,5,
Maria Perra
3,4,
Marta Giovanetti
6,7,
Alessandra Ciccozzi
8,
Andrea De Vito
9,
Angela Quirino
2,
Nadia Marascio
2,
Giovanni Matera
2,
Giordano Madeddu
9,
Marco Casu
4,
Daria Sanna
3,
Giancarlo Ceccarelli
10,11,
Massimo Ciccozzi
1 and
Fabio Scarpa
3,*add Show full author list remove Hide full author list
1
Unit of Medical Statistics and Molecular Epidemiology, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
2
Unit of Clinical Microbiology, Department of Health Sciences, “Magna Græcia” University of Catanzaro—“Renato Dulbecco” Teaching Hospital, 88100 Catanzaro, Italy
3
Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
4
Department of Veterinary Medicine, University of Sassari, 07100 Sassari, Italy
5
Department of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, 07100 Sassari, Italy
6
Department of Science and Technologies for Sustainable Development and One Health, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
7
Instituto Rene Rachou, Fundação Oswaldo Cruz-FIOCRUZ, Belo Horizonte 30190-009, MG, Brazil
8
Facoltà Dipartimentale di Scienze e Tecnologie per lo Sviluppo Sostenibile e One Health, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
9
Unit of Infectious Diseases, Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy
10
Department of Public Health and Infectious Diseases, University of Rome Sapienza, 00161 Rome, Italy
11
Azienda Ospedaliero Universitaria Umberto I, 00185 Rome, Italy
 
add Show full affiliation list
 
remove Hide full affiliation list
*
Authors to whom correspondence should be addressed.
Viruses 2025, 17(5), 664; https://doi.org/10.3390/v17050664
Submission received: 12 April 2025 / Revised: 24 April 2025 / Accepted: 25 April 2025 / Published: 1 May 2025
(This article belongs to the Section Human Virology and Viral Diseases)
Versions Notes

Abstract

Human T-lymphotropic viruses (HTLVs) are deltaretroviruses infecting millions of individuals worldwide, with HTLV-1 and HTLV-2 being the most widespread and clinically relevant types. HTLV-1 is associated with severe diseases such as adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), while HTLV-2 shows a lower pathogenic potential, with occasional links to neurological disorders. HTLV-3 and HTLV-4, identified in Central Africa, remain poorly characterized but are genetically close to their simian counterparts, indicating recent zoonotic transmission events. HTLVs replicate through a complex cycle involving cell-to-cell transmission and clonal expansion of infected lymphocytes. Viral persistence is mediated by regulatory and accessory proteins, notably Tax and HBZ in HTLV-1, which alter host cell signaling, immune responses, and genomic stability. Integration of proviral DNA into transcriptionally active regions of the host genome may contribute to oncogenesis and long-term viral latency. Differences in viral protein function and intracellular localization contribute to the distinct pathogenesis observed between HTLV-1 and HTLV-2. Geographically, HTLV-1 shows endemic clusters in southwestern Japan, sub-Saharan Africa, the Caribbean, South America, and parts of the Middle East and Oceania. HTLV-2 is concentrated among Indigenous populations in the Americas and people who inject drugs in Europe and North America. Transmission occurs primarily via breastfeeding, sexual contact, contaminated blood products, and, in some regions, zoonotic spillover. Diagnostic approaches include serological screening (ELISA, Western blot, LIA) and molecular assays (PCR, qPCR), with novel biosensor and AI-based methods under development. Despite advances in understanding viral biology, therapeutic options remain limited, and preventive strategies focus on transmission control. The long latency period, lack of effective treatments, and global neglect complicate public health responses, underscoring the need for increased awareness, research investment, and targeted interventions.
Keywords: HTLV; deltaretrovirus; adult T-cell leukemia/lymphoma; HAM/TSP; epidemiology; molecular diagnostics; genomics; genetic characterization HTLV; deltaretrovirus; adult T-cell leukemia/lymphoma; HAM/TSP; epidemiology; molecular diagnostics; genomics; genetic characterization

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MDPI and ACS Style

Branda, F.; Romano, C.; Pavia, G.; Bilotta, V.; Locci, C.; Azzena, I.; Deplano, I.; Pascale, N.; Perra, M.; Giovanetti, M.; et al. Human T-Lymphotropic Virus (HTLV): Epidemiology, Genetic, Pathogenesis, and Future Challenges. Viruses 2025, 17, 664. https://doi.org/10.3390/v17050664

AMA Style

Branda F, Romano C, Pavia G, Bilotta V, Locci C, Azzena I, Deplano I, Pascale N, Perra M, Giovanetti M, et al. Human T-Lymphotropic Virus (HTLV): Epidemiology, Genetic, Pathogenesis, and Future Challenges. Viruses. 2025; 17(5):664. https://doi.org/10.3390/v17050664

Chicago/Turabian Style

Branda, Francesco, Chiara Romano, Grazia Pavia, Viola Bilotta, Chiara Locci, Ilenia Azzena, Ilaria Deplano, Noemi Pascale, Maria Perra, Marta Giovanetti, and et al. 2025. "Human T-Lymphotropic Virus (HTLV): Epidemiology, Genetic, Pathogenesis, and Future Challenges" Viruses 17, no. 5: 664. https://doi.org/10.3390/v17050664

APA Style

Branda, F., Romano, C., Pavia, G., Bilotta, V., Locci, C., Azzena, I., Deplano, I., Pascale, N., Perra, M., Giovanetti, M., Ciccozzi, A., De Vito, A., Quirino, A., Marascio, N., Matera, G., Madeddu, G., Casu, M., Sanna, D., Ceccarelli, G., ... Scarpa, F. (2025). Human T-Lymphotropic Virus (HTLV): Epidemiology, Genetic, Pathogenesis, and Future Challenges. Viruses, 17(5), 664. https://doi.org/10.3390/v17050664

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