Research ArticleArenaviruses

siRNA Screen for Genes That Affect Junín Virus Entry Uncovers Voltage-Gated Calcium Channels as a Therapeutic Target

Science Translational Medicine  25 Sep 2013:
Vol. 5, Issue 204, pp. 204ra131
DOI: 10.1126/scitranslmed.3006827

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Abstract

New World hemorrhagic fever arenavirus infection results in 15 to 30% mortality in humans. We performed a high-throughput small interfering RNA screen with Junín virus glycoprotein-pseudotyped viruses to find potential host therapeutic targets. Voltage-gated calcium channel (VGCC) subunits, for which there are Food and Drug Administration (FDA)–approved drugs, were identified in the screen. Knockdown of VGCC subunits or treatment with channel blockers diminished Junín virus–cell fusion and entry into cells and thereby decreased infection. Gabapentin, an FDA-approved drug used to treat neuropathic pain that targets the α2δ2 subunit, inhibited infection of mice by the Candid 1 vaccine strain of the virus. These findings demonstrate that VGCCs play a role in virus infection and have the potential to lead to therapeutic intervention of New World arenavirus infection.

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