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

Year: 2013

Type: article

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.

Source: Science Translational Medicine

DOI: 10.1126/scitranslmed.3006827

Authors: Madakasira Lavanya, Christian D. Cuevas, Monica Thomas, Sara Cherry, Susan R. Ross

Institutions: University of Pennsylvania, Abramson Cancer Center

Language: English

Topic: Viral Infections and Vectors

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases