Human T‐cell leukemia virus type 1‐associated myelopathy/tropical spastic paraparesis and multiple sclerosis: Viral strategies and their implications

Abstract Human T‐cell leukemia virus type 1 (HTLV‐1)‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease of the central nervous system (CNS), particularly affecting the spinal cord, and is caused by HTLV‐1 infection. The biased geographic distribution of HTLV‐1‐infected individuals facilitated the early identification of a causal relationship between HTLV‐1 infection and related diseases soon after the discovery of the virus. In contrast, such a relationship would have been challenging to establish without this geographic clustering. Similarly, Epstein–Barr virus (EBV), which infects ~95% of the global population, has recently been implicated in the pathogenesis of multiple sclerosis (MS), another chronic inflammatory CNS disease. Advances in seroepidemiology, immunology, genomics, and biomarker research in large MS cohorts have shed light on EBV's critical role in disease development. These insights provide a framework for understanding the molecular mechanisms underlying both MS and HAM/TSP, which remain incompletely elucidated. In this review, we compare HTLV‐1 with EBV, focusing on their shared strategies for establishing long‐term latency in the host and their roles in CNS inflammation. By analyzing the relationship between HAM/TSP and MS through virological and molecular biological perspectives, we propose that both conditions may represent chronic inflammatory diseases of the CNS triggered by viral infections. This hypothesis offers a novel perspective on the pathogenesis of these diseases. Finally, we discuss current challenges and future directions in the treatment and prevention of HAM/TSP and MS.