BioGPS Featured Article – siRNA screen for genes that affect Junin virus entry uncovers voltage-gated calcium channels as a therapeutic target

BioGPS has become the valuable resource that it is because of the contributions from our wonderful user community. Thank you for contributing plugins, suggestions, and ideas–all of which have improved BioGPS for everyone. In order to celebrate the contributions of BioGPS users to the scientific research community, this series will feature publications and articles generated by BioGPS users. We sincerely hope you will join us in celebrating the fascinating work that YOU do.

This week, we will feature an article from a team at the University of Pennsylvania studying new world arenavirus infections: siRNA screen for genes that affect Junin virus entry uncovers voltage-gated calcium channels as a therapeutic target. by Madakasira Lavanya, Christian D. Cuevas, Monica Thomas, Sara Cherry, and Susan R. Ross.

Dr. Susan R. Ross, one of the two principle investigators involved, kindly answered our inquiries for this series.

  1. Who is the team behind the work that was published in siRNA screen for genes that affect Junin virus entry uncovers voltage-gated calcium channels as a therapeutic target?.
    Two postdoctoral fellows, Lavanya Madakasira and Christian Cuevas, an undergraduate Monica Thomas (currently a grad student at Duke University), Sara Cherry and Susan Ross, faculty members in the dept. of Microbiology at the Perelman School of Medicine, University of Pennsylvania.
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  3. What inspired the work published in siRNA screen for genes that affect Junin virus entry uncovers voltage-gated calcium channels as a therapeutic target?
    My lab had been studying how Junin virus enters cells. Sara Cherry’s lab has pioneered the use of siRNA screening to study virus infection. We collaborated to use siRNA screening to identify novel cellular proteins involved in Junin virus infection. We felt that this could lead to the identification of new therapeutic targets for infection.
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  5. Please provide a brief summary of the findings reported in your article, siRNA screen for genes that affect Junin virus entry uncovers voltage-gated calcium channels as a therapeutic target.
    New world hemorrhagic fever arenaviruses infection of humans results in 15-30% mortality. We performed a high throughput siRNA screen with Junín virus glycoprotein-pseudotyped viruses to find potential host therapeutic targets. Voltage-gated calcium channels (VGCC) subunits, for which there are 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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  7. How did the team learn about BioGPS?
    We’ve been using it since the Symatlas days.
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  9. How did your team utilize BioGPS in this research?
    We used BioGPS to look at the expression of genes identified in the siRNA screen as anti- or pro-viral for Junin virus infection in different tissues and cell lines.
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  11. What are some future directions for the team behind this research?
    We are working on understanding the mechanism by which VGCCs participate in Junin virus entry, as well as testing whether VGCC blockers can be used therapeutically to decrease infection.

Thanks again to Dr. Susan R. Ross for taking the time to answer our questions and for being a long-time user of BioGPS. We really look forward to the publication of the aforementioned manuscripts-in-prep. Click here to read their fascinating article. Have a look because these awesome researchers have made their compelling research open access–so you can read the whole exciting article for free!

Used BioGPS and cited it in your publication? Let us know! We would love to feature YOUR work, no matter how long ago it was published. BioGPS Featured Article Series only started recently, but we know your contributions to science is ongoing.


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