Central Virology Laboratory, Public Health Services, Ministry of Health and Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel.
Virus Res. 2012 Jun;166(1-2):68-76. doi: 10.1016/j.virusres.2012.03.004. Epub 2012 Mar 14.
There are currently no effective drugs to treat serious complications caused by WNV infection. The inhibition of WNV by the pluripotent immunomodulator AS101 [ammonium trichloro(dioxyethylene-0-0')tellurate] was evaluated in vitro and in vivo, and its mechanism was explored. Adding AS101 to Vero cells 1h or 5 min before infection increased cell survival from 21% to 84% and decreased plaque formation by 87% and virus yield by 2 logs. Following infection, high titer of WNV remained in the culture supernatants indicating interference with virus cell attachment. The binding of α(V)β(3) integrin to WNV and of Vero cells to anti-α(V)β(3) antibody were inhibited by AS101, suggesting that AS101 may block this cellular WNV receptor. Daily treatment of mice with AS101 starting 1 day before lethal infection with WNV resulted in 48% survival. However, treatment beginning 3 days post infection resulted only in 16% survival. Similarly, a single dose of anti-WNV IVIG three days post infection resulted in 16% survival compared to 100% if IVIG was given on the same day of infection or 1 day later. However, when mice received combined treatment with AS101 and IVIG starting 3 days post infection, an additive effect of 33% survival was observed. Our study suggests that AS101 has a potential preventive and therapeutic effect against WNV infection.
目前还没有有效的药物来治疗 WNV 感染引起的严重并发症。多能免疫调节剂 AS101（三氯（二氧乙撑-0-0'）碲酸铵）在体外和体内抑制 WNV 的作用，并探讨其机制。在感染前 1 小时或 5 分钟向 Vero 细胞中添加 AS101，可将细胞存活率从 21%提高到 84%，降低 87%的斑块形成率和 2 个对数的病毒产量。感染后，WNV 的高滴度仍存在于培养上清液中，表明干扰了病毒与细胞的附着。AS101 抑制了 α(V)β(3)整联蛋白与 WNV 的结合以及 Vero 细胞与抗-α(V)β(3)抗体的结合，表明 AS101 可能阻断这种细胞 WNV 受体。在致死性 WNV 感染前 1 天开始用 AS101 对小鼠进行每日治疗，可使 48%的小鼠存活。然而，在感染后 3 天开始治疗仅导致 16%的小鼠存活。同样，在感染后 3 天给予一剂抗 WNV IVIG 仅导致 16%的小鼠存活，而如果在感染当天或 1 天后给予 IVIG，则有 100%的小鼠存活。然而，当小鼠在感染后 3 天开始联合使用 AS101 和 IVIG 进行治疗时，观察到 33%的存活具有相加作用。我们的研究表明，AS101 对 WNV 感染具有潜在的预防和治疗作用。
