Fucoidan therapy decreases the proviral load in patients with human T-lymphotropic virus type-1-associated neurological disease

Natsumi Araya, Katsunori Takahashi, Tomoo Sato, Tatsufumi Nakamura, Chika Sawa, Daisuke Hasegawa, Hitoshi Ando, Satoko Aratani, Naoko Yagishita, Ryoji Fujii, Hiroshi Oka, Kusuki Nishioka (+3 others)
2011 Antiviral Therapy  
Human T-lymphotropic virus type-1 (HTLV-1) is a human retrovirus that causes HTLV-1associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukaemia (ATL). A higher viral load in individuals with HTLV-1 infection increases their risk of developing HAM/TSP and ATL. Moreover, the high proviral load is associated with the clinical progression of HAM/TSP. Reduction of the number of HTLV-1-infected cells is therefore crucial for preventing and treating HTLV-1-associated
more » ... -associated diseases. Recently, fucoidan, a complex sulphated polysaccharide derived from marine seaweed, has been demonstrated to exert inhibitory effects on HTLV-1 infection in vitro. In this study, we examined the in vivo effects of fucoidan on HTLV-1 infection. Methods: In this single-centre open-label trial, 13 patients with HAM/TSP were treated with 6 g fucoidan daily for 6-13 months. The HTLV-1 proviral DNA load and frequencies of HTLV-1-specific CD8 + T-cells, natural killer cells, invariant natural killer T-cells and dendritic cells in the peripheral blood were analysed. Furthermore, the in vitro inhibitory effect of fucoidan on cell-tocell HTLV-1 infection was examined by using luciferase reporter cell assays. Results: Fucoidan inhibited the cell-to-cell transmission of HTLV-1 in vitro. Furthermore, fucoidan therapy resulted in a 42.4% decrease in the HTLV-1 proviral load without affecting the host immune cells. During the treatment, no exacerbation was observed. Four patients with HAM/TSP developed diarrhoea, which improved immediately after stopping fucoidan administration. Conclusions: Fucoidan is a new potential therapeutic agent for the prevention and treatment of HTLV-1associated diseases. Human T-lymphotropic virus type-1 (HTLV-1) is an exogenous human retrovirus that infects 10-20 million people worldwide [1] . Although most of the infected individuals are lifelong asymptomatic carriers, 3-5% of the infected population develop a T-cell malignancy called adult T-cell leukaemia (ATL) and another 0.25-3% develop a chronic progressive inflammatory neurological disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) [2] [3] [4] . One of the most important pathogenic factors in HAM/TSP is the increased HTLV-1 proviral load in peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid [5] [6] [7] , which suggests that viral control is inadequate in the affected individuals. Furthermore, a high HTLV-1 proviral load increases the risk of development of HAM/TSP and ATL [5, 8] . Therefore, the identification of agents that can reduce the HTLV-1 proviral load is crucial for preventing and treating HTLV-1-associated disorders. Fucoidan, a complex sulphated polysaccharide derived from marine seaweed, exerts various biological effects on mammalian cells and viral infection [9, 10] . Regarding HTLV-1 infection, previous studies have shown that fucoidan inhibits both the adhesion of HTLV-1-infected
doi:10.3851/imp1699 pmid:21311112 fatcat:rrfkri6nrrbihlucl4adhrzsmu