HTLV-1 Infection and Associated Clinical Manifestations

Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus infecting an estimated 10–20 million individuals worldwide, primarily in regions including Japan, the Caribbean, parts of Central and South America, intertropical Africa and the Middle East. Following transmission by breast-feeding, sexual contact or blood exposure, HTLV-1 establishes a lifelong infection of CD4+ T lymphocytes, often remaining asymptomatic. A minority of carriers develop adult T-cell leukaemia/lymphoma (ATL), characterised by aggressive T-cell malignancy, or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic inflammatory disorder of the spinal cord leading to progressive motor dysfunction. Less frequent manifestations include infectious dermatitis, uveitis and pulmonary disease. Disease risk correlates with proviral load, host genetic factors and immunological responses. Viral regulatory proteins such as Tax and HBZ dysregulate host signalling pathways, promoting cell proliferation, inflammatory cytokine release and genetic instability. Clinical management remains supportive, with emerging interventions targeting viral gene products, host kinases and transmission pathways. Global initiatives to implement antenatal screening, avoid mother-to-child transmission and explore antiretroviral prophylaxis are critical to reduce the burden of HTLV-1-related diseases.

Research from Nature Portfolio

Recent studies have uncovered a critical dependency of HTLV-1-transformed T cells on the receptor tyrosine kinase KDR. A kinome-wide screen identified KDR as essential for stabilising the viral oncoprotein Tax, thereby sustaining NF-κB activation and cell survival. Pharmacological inhibition of KDR triggered Tax degradation through autophagy, compromised NF-κB signalling and induced apoptosis selectively in HTLV-1-infected cells. This approach also reduced viral transmission in co-culture assays. These findings reveal KDR as a novel host target for disrupting HTLV-1 persistence and offer a potential therapeutic strategy to attenuate both ATL and HAM/TSP.

HTLV-1 Infection and Associated Clinical Manifestations publication trend

The graph below shows the total number of articles in htlv-1 infection and associated clinical manifestations across all publications each year (not limited to Nature Index journals).

Technical terms

Adult T-cell leukaemia/lymphoma (ATL): An aggressive malignancy of HTLV-1-infected T cells characterised by lymphadenopathy, skin lesions and hypercalcaemia.

HAM/TSP: HTLV-1-associated myelopathy/tropical spastic paraparesis, a chronic inflammatory disease causing progressive spasticity and sensory disturbance in the lower limbs.

Proviral load: The number of viral DNA copies integrated into host genomes per peripheral blood mononuclear cells, used as a marker of disease risk.

Tax oncoprotein: A viral regulatory protein that activates NF-κB and other pathways to promote infected cell survival and persistence.

Small extracellular vesicles (sEV): Membrane-bound vesicles released by cells that carry proteins, RNAs and viral components to modulate distant microenvironments.

Receptor tyrosine kinase KDR: Also known as VEGFR-2, a host enzyme that, when inhibited, destabilises Tax and impairs HTLV-1-infected cell viability.

References

1. Economic analysis of antenatal screening for human T-cell lymphotropic virus type 1 in Brazil: an open access cost-utility model. The Lancet Global Health (2023).
2. The tyrosine kinase KDR is essential for the survival of HTLV-1-infected T cells by stabilizing the Tax oncoprotein. Nature Communications (2024).
3. HTLV‐1 infected T cells cause bone loss via small extracellular vesicles. Journal of Extracellular Vesicles (2024).
4. Human T-lymphotropic virus type 1 and antiretroviral therapy: practical considerations for pre-exposure and post-exposure prophylaxis, transmission prevention, and mitigation of severe disease. The Lancet Microbe (2024).
5. Clinical Pathophysiology of Human T-Lymphotropic Virus-Type 1-Associated Myelopathy/Tropical Spastic Paraparesis. Frontiers in Microbiology (2012).
6. HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma—A Tale of Two Proteins: Tax and HBZ. Viruses (2016).