Open AccessDigoxin Suppresses HIV-1 Replication by Altering Viral RNA Processing
Author(s) -
Raymond Wong,
Ahalya Balachandran,
Mario Ostrowski,
Alan Cochrane
Publication year - 2013
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1003241
Subject(s) - digoxin , viral replication , rna , small interfering rna , biology , rna splicing , in vitro , viral load , virology , human immunodeficiency virus (hiv) , virus , medicine , genetics , gene , heart failure
To develop new approaches to control HIV-1 replication, we examined the capacity of recently described small molecular modulators of RNA splicing for their effects on viral RNA metabolism. Of the drugs tested, digoxin was found to induce a dramatic inhibition of HIV-1 structural protein synthesis, a response due, in part, to reduced accumulation of the corresponding viral mRNAs. In addition, digoxin altered viral RNA splice site use, resulting in loss of the essential viral factor Rev. Digoxin induced changes in activity of the CLK family of SR protein kinases and modification of several SR proteins, including SRp20 and Tra2β, which could account for the effects observed. Consistent with this hypothesis, overexpression of SRp20 elicited changes in HIV-1 RNA processing similar to those observed with digoxin. Importantly, digoxin was also highly active against clinical strains of HIV-1 in vitro , validating this novel approach to treatment of this infection.