Nuclear localization of dengue virus (DENV) 1-4 non-structural protein 5; protection against all 4 DENV serotypes by the inhibitor Ivermectin

M Y F Tay, Johanna Elisabeth Fraser, W K K Chan, Nicole J Moreland, Abhay P Rathore, Chieh-Huei Wang, Subhash G Vasudevan, David Andrew Jans

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156 Citations (Scopus)

Abstract

Infection by one of the 4 distinct serotypes of dengue virus (DENV) threatens >40 of the world s population, with no efficacious vaccine or antiviral agent currently available. DENV replication through the virus-encoded nonstructural protein (NS) 5 protein occurs in the infected cell cytoplasm, but NS5 from DENV2 has thus far been shown to localize strongly in the nucleus throughout infection. Here we use specific antibodies cross-reactive with NS5 from DENV1-4 to demonstrate nuclear localization of NS5 from all DENV serotypes for the first time in both infected as well as transfected cells, although to differing extents. The small-molecule inhibitor Ivermectin was inhibitory towards both DENV 1 and 2 NS5 interaction with its nuclear transporter importin alpha/beta in vitro, and protected against infection from DENV1-4. Ivermectin thus has potential in the clinical setting as a dengue antiviral.
Original languageEnglish
Pages (from-to)301 - 306
Number of pages6
JournalAntiviral Research
Volume99
Issue number3
DOIs
Publication statusPublished - 2013

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