A cellular microRNA mediates antiviral defense in human cells

Science. 2005 Apr 22;308(5721):557-60. doi: 10.1126/science.1108784.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / physiology*
  • Arabidopsis / genetics
  • Cell Line
  • Cricetinae
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • HeLa Cells
  • Humans
  • MicroRNAs / physiology*
  • Oligonucleotides, Antisense
  • Plants, Genetically Modified
  • Protein Biosynthesis
  • RNA Interference*
  • RNA, Viral
  • Retroviridae Proteins / genetics
  • Retroviridae Proteins / metabolism
  • Spumavirus / genetics*
  • Spumavirus / physiology*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transfection
  • Virus Replication

Substances

  • Antiviral Agents
  • DNA-Binding Proteins
  • MicroRNAs
  • Oligonucleotides, Antisense
  • RNA, Viral
  • Retroviridae Proteins
  • Trans-Activators
  • bel1 protein, Human foamy virus
  • Green Fluorescent Proteins