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SiRNA screen for genes that affect Junin virus entry uncovers voltage-gated calcium channels as a therapeutic target.

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 ???? 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.

SUBMITTER: Lavanya M

PROVIDER: S-EPMC4104171 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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siRNA screen for genes that affect Junín virus entry uncovers voltage-gated calcium channels as a therapeutic target.

Lavanya Madakasira M Cuevas Christian D CD Thomas Monica M Cherry Sara S Ross Susan R SR

Science translational medicine 20130901 204

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 ...[more]

PMID: 24068738

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