tetano
Editor, Senior Moderator
Cell Rep. 2015 Jun 9. pii: S2211-1247(15)00568-9. doi: 10.1016/j.celrep.2015.05.032. [Epub ahead of print]
[h=1]In Vivo RNAi Screening Identifies MDA5 as a Significant Contributor to the Cellular Defense against Influenza A Virus.[/h] Benitez AA[SUP]1[/SUP], Panis M[SUP]1[/SUP], Xue J[SUP]2[/SUP], Varble A[SUP]1[/SUP], Shim JV[SUP]1[/SUP], Frick AL[SUP]3[/SUP], L?pez CB[SUP]2[/SUP], Sachs D[SUP]4[/SUP], tenOever BR[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Responding to an influenza A virus (IAV) infection demands an effective intrinsic cellular defense strategy to slow replication. To identify contributing host factors to this defense, we exploited the host microRNA pathway to perform an in vivo RNAi screen. To this end, IAV, lacking a functional NS1 antagonist, was engineered to encode individual siRNAs against antiviral host genes in an effort to rescue attenuation. This screening platform resulted in the enrichment of strains targeting virus-activated transcription factors, specific antiviral effectors, and intracellular pattern recognition receptors (PRRs). Interestingly, in addition to RIG-I, the PRR for IAV, a virus with the capacity to silence MDA5 also emerged as a dominant strain in wild-type, but not in MDA5-deficient mice. Transcriptional profiling of infected knockout cells confirmed RIG-I to be the primary PRR for IAV but implicated MDA5 as a significant contributor to the cellular defense against influenza A virus.
Copyright ? 2015 The Authors. Published by Elsevier Inc. All rights reserved.
PMID: 26074083 [PubMed - as supplied by publisher]
[h=1]In Vivo RNAi Screening Identifies MDA5 as a Significant Contributor to the Cellular Defense against Influenza A Virus.[/h] Benitez AA[SUP]1[/SUP], Panis M[SUP]1[/SUP], Xue J[SUP]2[/SUP], Varble A[SUP]1[/SUP], Shim JV[SUP]1[/SUP], Frick AL[SUP]3[/SUP], L?pez CB[SUP]2[/SUP], Sachs D[SUP]4[/SUP], tenOever BR[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Responding to an influenza A virus (IAV) infection demands an effective intrinsic cellular defense strategy to slow replication. To identify contributing host factors to this defense, we exploited the host microRNA pathway to perform an in vivo RNAi screen. To this end, IAV, lacking a functional NS1 antagonist, was engineered to encode individual siRNAs against antiviral host genes in an effort to rescue attenuation. This screening platform resulted in the enrichment of strains targeting virus-activated transcription factors, specific antiviral effectors, and intracellular pattern recognition receptors (PRRs). Interestingly, in addition to RIG-I, the PRR for IAV, a virus with the capacity to silence MDA5 also emerged as a dominant strain in wild-type, but not in MDA5-deficient mice. Transcriptional profiling of infected knockout cells confirmed RIG-I to be the primary PRR for IAV but implicated MDA5 as a significant contributor to the cellular defense against influenza A virus.
Copyright ? 2015 The Authors. Published by Elsevier Inc. All rights reserved.
PMID: 26074083 [PubMed - as supplied by publisher]