Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
3428718 | Virus Research | 2012 | 9 Pages |
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 1 h 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 αVβ3 integrin to WNV and of Vero cells to anti-αVβ3 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.
► AS101 significantly inhibited WNV plaque formation and virus yield and increased Vero cell survival. ► AS101 inhibited binding of αVβ3 integrin to WNV and of anti-αVβ3 to Vero cells. ► AS101 interacts with αVβ3 integrin. ► Daily treatment with AS101 protected mice from a lethal dose of WNV by 48%.