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An In Vivo RNAi Screening Approach to Identify Host Determinants of Virus Replication

Lookup NU author(s): Dr Ruth Rodriguez Barrueco

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Abstract

RNA interference (RNAi) has been extensively used to identify host factors affecting virus infection but requires exogenous delivery of short interfering RNAs (siRNAs), thus limiting the technique to nonphysiological infection models and a single defined cell type. We report an alternative screening approach using siRNA delivery via infection with a replication-competent RNA virus. In this system, natural selection, defined by siRNA production, permits the identification of host restriction factors through virus enrichment during a physiological infection. We validate this approach with a large-scale siRNA screen in the context of an in vivo alphavirus infection. Monitoring virus evolution across four independent screens identified two categories of enriched siRNAs: specific effectors of the direct antiviral arsenal and host factors that indirectly dampened the overall antiviral response. These results suggest that pathogenicity may be defined by the ability of the virus to antagonize broad cellular responses and specific antiviral factors.

Publication metadata

Author(s): Varble A, Benitez AA, Scgmid S, Sachs D, Shim JV, Rodriguez-Barrueco R, Panis M, Crumiller M, Silva JM, Sachidanandam R, tenOever BR

Publication type: Article

Publication status: Published

Journal: Cell Host & Microbe

Year: 2013

Volume: 14

Issue: 3

Pages: 346-356

Print publication date: 11/09/2013

Online publication date: 11/09/2013

ISSN (print): 1931-3128

ISSN (electronic): 1934-6069

Publisher: Cell Press

URL: http://dx.doi.org/10.1016/j.chom.2013.08.007

DOI: 10.1016/j.chom.2013.08.007

PubMed id: 24034620

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