A cellular microRNA mediates antiviral defense in human cells.
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.
Lecellier
Charles-Henri
CH
CNRS Unité Propre de Recherche (UPR) 2357, Institut de Biologie Moléculaire des Plantes, 12 rue du Général Zimmer, 67084 Strasbourg Cedex, France. charles.lecellier@infobiogen.fr
Dunoyer
Patrice
P
Arar
Khalil
K
Lehmann-Che
Jacqueline
J
Eyquem
Stephanie
S
Himber
Christophe
C
Saïb
Ali
A
Voinnet
Olivier
O
D000818:Animals; D000998:Antiviral Agents / Q000502:physiology*; D017360:Arabidopsis / Q000235:genetics; D002460:Cell Line; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D016376:Oligonucleotides, Antisense; D030821:Plants, Genetically Modified; D014176:Protein Biosynthesis; D034622:RNA Interference; D012367:RNA, Viral; D012191:Retroviridae Proteins / Q000235:genetics / Q000378:metabolism; D016092:Spumavirus / Q000235:genetics* / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014779:Virus Replication
D000998:Antiviral Agents; D004268:DNA-Binding Proteins; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D012367:RNA, Viral; D012191:Retroviridae Proteins; D015534:Trans-Activators; C074061:bel1 protein, Human foamy virus; D049452:Green Fluorescent Proteins