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Science 308 (5721): 557-560

Copyright © 2005 by the American Association for the Advancement of Science

A Cellular MicroRNA Mediates Antiviral Defense in Human Cells

Charles-Henri Lecellier,1* Patrice Dunoyer,1 Khalil Arar,2 Jacqueline Lehmann-Che,3 Stephanie Eyquem,4 Christophe Himber,1 Ali Saïb,3 Olivier Voinnet1*

Abstract: In eukaryotes, 21- to 24-nucleotide-long RNAs engage in sequence-specific interactions that inhibit gene expression by RNA silencing. This process has regulatory roles involving microRNAs and, in plants and insects, it also forms the basis of a defense mechanism directed by small interfering RNAs that derive from replicative or integrated viral genomes. We show that a cellular microRNA effectively restricts the accumulation of the retrovirus primate foamy virus type 1 (PFV-1) in human cells. PFV-1 also encodes a protein, Tas, that suppresses microRNA-directed functions in mammalian cells and displays cross-kingdom antisilencing activities. Therefore, through fortuitous recognition of foreign nucleic acids, cellular microRNAs have direct antiviral effects in addition to their regulatory functions.

1 CNRS Unité Propre de Recherche (UPR) 2357, Institut de Biologie Moléculaire des Plantes, 12 rue du Général Zimmer, 67084 Strasbourg Cedex, France.
2 Proligo, Paris, France.
3 CNRS UPR9051, Hôpital St-Louis, Paris, France.
4 INSERM U462, Hôpital St-Louis, Paris, France.

Note added in proof: Recent findings indicate that a single 8-oligonucleotide seed (small RNA positions 1 to 8 from the 5' end) is sufficient to confer strong regulation by animals miRNAs. Thus, fortuitous targeting of foreign RNAs by cellular miRNAs could be widespread (21, 22).

* To whom correspondence should be addressed. E-mail: charles.lecellier{at} (C.-H.L.); olivier. voinnet{at} (O.V.)

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