Araya Natsumi, Takahashi Katsunori, Sato Tomoo, Nakamura Tatsufumi, Sawa Chika, Hasegawa Daisuke, Ando Hitoshi, Aratani Satoko, Yagishita Naoko, Fujii Ryoji, Oka Hiroshi, Nishioka Kusuki, Nakajima Toshihiro, Mori Naoki, Yamano Yoshihisa
Department of Molecular Medical Science, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Japan.
Antivir Ther. 2011;16(1):89-98. doi: 10.3851/IMP1699.
Human T-lymphotropic virus type-1 (HTLV-1) is a human retrovirus that causes HTLV-1-associated 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 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.
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-to-cell HTLV-1 infection was examined by using luciferase reporter cell assays.
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.
Fucoidan is a new potential therapeutic agent for the prevention and treatment of HTLV-1-associated diseases.
人类嗜T淋巴细胞病毒1型(HTLV-1)是一种人类逆转录病毒,可导致HTLV-1相关脊髓病/热带痉挛性截瘫(HAM/TSP)和成人T细胞白血病(ATL)。HTLV-1感染者体内较高的病毒载量会增加其患HAM/TSP和ATL的风险。此外,高前病毒载量与HAM/TSP的临床进展相关。因此,减少HTLV-1感染细胞的数量对于预防和治疗HTLV-1相关疾病至关重要。最近,岩藻依聚糖是一种从海藻中提取的复杂硫酸化多糖,已被证明在体外对HTLV-1感染具有抑制作用。在本研究中,我们研究了岩藻依聚糖对HTLV-1感染的体内作用。
在这项单中心开放标签试验中,13例HAM/TSP患者每天接受6克岩藻依聚糖治疗,持续6至13个月。分析外周血中HTLV-1前病毒DNA载量以及HTLV-1特异性CD8(+)T细胞、自然杀伤细胞、不变自然杀伤T细胞和树突状细胞的频率。此外,通过荧光素酶报告细胞测定法检测岩藻依聚糖对细胞间HTLV-1感染的体外抑制作用。
岩藻依聚糖在体外抑制了HTLV-1的细胞间传播。此外,岩藻依聚糖治疗使HTLV-1前病毒载量降低了42.4%,且不影响宿主免疫细胞。治疗期间未观察到病情加重。4例HAM/TSP患者出现腹泻,在停止服用岩藻依聚糖后立即好转。
岩藻依聚糖是预防和治疗HTLV-1相关疾病的一种新的潜在治疗药物。