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An in vivo RNAi screening approach to identify host determinants of virus replication.

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.

journal_name

Cell Host Microbe

journal_title

Cell host & microbe

authors

Varble A,Benitez AA,Schmid S,Sachs D,Shim JV,Rodriguez-Barrueco R,Panis M,Crumiller M,Silva JM,Sachidanandam R,tenOever BR

doi

10.1016/j.chom.2013.08.007

subject

Has Abstract

pub_date

2013-09-11 00:00:00

pages

346-56

issue

3

eissn

1931-3128

issn

1934-6069

pii

S1931-3128(13)00289-8

journal_volume

14

pub_type

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