Abstract:
: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.
journal_name
Virus Resjournal_title
Virus researchauthors
Indenbaum V,Bin H,Makarovsky D,Weil M,Shulman LM,Albeck M,Sredni B,Mendelson Edoi
10.1016/j.virusres.2012.03.004subject
Has Abstractpub_date
2012-06-01 00:00:00pages
68-76issue
1-2eissn
0168-1702issn
1872-7492pii
S0168-1702(12)00096-2journal_volume
166pub_type
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