title: Cross-species comparative analysis of Dicer proteins during Sindbis virus infection.
abstract: In plants and invertebrates RNA silencing is a major defense mechanism against virus infections. The first event in RNA silencing is dicing of long double stranded RNAs into small interfering RNAs (siRNAs). The Dicer proteins involved in this process are phylogenetically conserved and have the same domain organization. Accordingly, the production of viral derived siRNAs has also been observed in the mouse, but only in restricted cell types. To gain insight on this restriction, we compare the dicing activity of human Dicer and fly Dicer-2 in the context of Sindbis virus (SINV) infection. Expression of human Dicer in flies inefficiently rescues the production of viral siRNAs but confers some protection against SINV. Conversely, expression of Dicer-2 in human cells allows the production of viral 21 nt small RNAs. However, this does not confer resistance to viral infection, but on the contrary results in stronger accumulation of viral RNA. We further show that Dicer-2 expression in human cells perturbs interferon (IFN) signaling pathways and antagonizes protein kinase R (PKR)-mediated antiviral immunity. Overall, our data suggest that a functional incompatibility between the Dicer and IFN pathways explains the predominance of the IFN response in mammalian somatic cells.
authors.affiliation: Architecture and Reactivity of RNA, Institut de Biologie Moléculaire et Cellulaire du CNRS, Université de Strasbourg, 15 rue René Descartes, 67084 Strasbourg, France.
authors.forename: Erika
authors.initials: E
authors.lastname: Girardi
authors.affiliation: Architecture and Reactivity of RNA, Institut de Biologie Moléculaire et Cellulaire du CNRS, Université de Strasbourg, 15 rue René Descartes, 67084 Strasbourg, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lefèvre
authors.affiliation: Architecture and Reactivity of RNA, Institut de Biologie Moléculaire et Cellulaire du CNRS, Université de Strasbourg, 15 rue René Descartes, 67084 Strasbourg, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Chane-Woon-Ming
authors.affiliation: Immune response and development in insects, Institut de Biologie Moléculaire et Cellulaire du CNRS, Université de Strasbourg, 15 rue René Descartes, 67084 Strasbourg, France.
authors.forename: Simona
authors.initials: S
authors.lastname: Paro
authors.affiliation: Immune response and development in insects, Institut de Biologie Moléculaire et Cellulaire du CNRS, Université de Strasbourg, 15 rue René Descartes, 67084 Strasbourg, France.
authors.forename: Bill
authors.initials: B
authors.lastname: Claydon
authors.affiliation: Immune response and development in insects, Institut de Biologie Moléculaire et Cellulaire du CNRS, Université de Strasbourg, 15 rue René Descartes, 67084 Strasbourg, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Imler
authors.affiliation: Immune response and development in insects, Institut de Biologie Moléculaire et Cellulaire du CNRS, Université de Strasbourg, 15 rue René Descartes, 67084 Strasbourg, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Meignin
authors.affiliation: Architecture and Reactivity of RNA, Institut de Biologie Moléculaire et Cellulaire du CNRS, Université de Strasbourg, 15 rue René Descartes, 67084 Strasbourg, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Pfeffer
mesh_terms: D018354:Alphavirus Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D000818:Animals; D030801:Animals, Genetically Modified; D002460:Cell Line; D004330:Drosophila; D015870:Gene Expression; D020868:Gene Silencing; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007372:Interferons / Q000378:metabolism; D034622:RNA Interference; D058727:RNA, Small Untranslated / Q000235:genetics; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012845:Sindbis Virus / Q000235:genetics*
chemical_list: D058727:RNA, Small Untranslated; D007372:Interferons; D043244:Ribonuclease III