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

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 α/β in vitro, and protected against infection from DENV1-4. Ivermectin thus has potential in the clinical setting as a dengue antiviral.

• Authors: M Y F Tay, J E Fraser, W K K Chan, N J Moreland, A P Rathore, C Wang, S G Vasudevan, D A Jans
• Journal: Antiviral research (Antiviral Res) Vol. 99 Issue 3 Pg. 301-6 (Sep 2013) ISSN: 1872-9096 [Electronic] Netherlands
• PMID: 23769930 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Antiviral Agents
• NS5 protein, dengue virus
• Viral Nonstructural Proteins
• Ivermectin

Topics

• Antiviral Agents (pharmacology)
• Cell Nucleus (virology)
• Cytoplasm (virology)
• Dengue (drug therapy, virology)
• Dengue Virus (classification, drug effects, genetics, metabolism)
• Humans
• Ivermectin (pharmacology)
• Protein Transport (drug effects)
• Viral Nonstructural Proteins (genetics, metabolism)