Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, Centre National de la Recherche Scientifique (CNRS) URA 3015, Institut Pasteur, Paris, France.
Blood. 2010 Nov 11;116(19):3802-8. doi: 10.1182/blood-2010-02-270751. Epub 2010 Jun 29.
Approximately 3% of all human T-lymphotropic virus type 1 (HTLV-1)-infected persons will develop a disabling inflammatory disease of the central nervous system known as HTLV-1-associated myelopathy/tropical spastic paraparesis, against which there is currently no efficient treatment. As correlation exists between the proviral load (PVL) and the clinical status of the carrier, it is thought that diminishing the PVL could prevent later occurrence of the disease. We have conducted a study combining valproate, an inhibitor of histone deacetylases, and azidothymidine, an inhibitor of reverse transcriptase, in a series of baboons naturally infected with simian T-lymphotropic virus type 1 (STLV-1), whose PVL was equivalent to that of HTLV-1 asymptomatic carriers. We show that the combination of drugs caused a strong decrease in the PVL and prevented the transient rise in PVL that is seen after treatment with histone deacetylases alone. We then demonstrate that the PVL decline was associated with an increase in the STLV-1-specific cytotoxic T-cell population. We conclude that combined treatment with valproate to induce viral expression and azidothymidine to prevent viral propagation is a safe and effective means to decrease PVL in vivo. Such treatments may be useful to reduce the risk of HAM/TSP in asymptomatic carriers with a high PVL.
约 3%的人类 T 淋巴细胞白血病病毒 1 型（HTLV-1）感染者会患上一种中枢神经系统的致残性炎症疾病，即 HTLV-1 相关脊髓病/热带痉挛性截瘫，目前尚无有效的治疗方法。由于前病毒载量（PVL）与携带者的临床状况之间存在相关性，因此人们认为降低 PVL 可以预防疾病的后期发生。我们对一组自然感染猴 T 淋巴细胞白血病病毒 1 型（STLV-1）的狨猴进行了一项研究，联合使用组蛋白去乙酰化酶抑制剂丙戊酸和逆转录酶抑制剂叠氮胸苷。这些狨猴的 PVL 与 HTLV-1 无症状携带者相当。我们发现，这种药物联合使用可显著降低 PVL，并可防止单独使用组蛋白去乙酰化酶治疗后出现的 PVL 短暂升高。然后，我们证明 PVL 的下降与 STLV-1 特异性细胞毒性 T 细胞群体的增加有关。我们的结论是，用丙戊酸诱导病毒表达，用叠氮胸苷防止病毒复制的联合治疗是一种安全有效的降低体内 PVL 的方法。这种治疗方法可能有助于降低高 PVL 的无症状携带者发生 HAM/TSP 的风险。
