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Short interfering RNA confers intracellular antiviral immunity in human cells

Author

Listed:
  • Leonid Gitlin

    (University of California
    Program in Neuroscience, University of California)

  • Sveta Karelsky

    (University of California)

  • Raul Andino

    (University of California)

Abstract

Gene silencing mediated by double-stranded RNA (dsRNA) is a sequence-specific, highly conserved mechanism in eukaryotes. In plants, it serves as an antiviral defence mechanism1,2,3. Animal cells also possess this machinery but its specific function is unclear4,5,6,7,8,9,10. Here we demonstrate that dsRNA can effectively protect human cells against infection by a rapidly replicating and highly cytolytic RNA virus. Pre-treatment of human and mouse cells with double-stranded, short interfering RNAs (siRNAs) to the poliovirus genome markedly reduces the titre of virus progeny and promotes clearance of the virus from most of the infected cells. The antiviral effect is sequence-specific and is not attributable to either classical antisense mechanisms or to interferon and the interferon response effectors protein kinase R (PKR) and RNaseL. Protection is the result of direct targeting of the viral genome by siRNA, as sequence analysis of escape virus (resistant to siRNAs) reveals one nucleotide substitution in the middle of the targeted sequence. Thus, siRNAs elicit specific intracellular antiviral resistance that may provide a therapeutic strategy against human viruses.

Suggested Citation

  • Leonid Gitlin & Sveta Karelsky & Raul Andino, 2002. "Short interfering RNA confers intracellular antiviral immunity in human cells," Nature, Nature, vol. 418(6896), pages 430-434, July.
  • Handle: RePEc:nat:nature:v:418:y:2002:i:6896:d:10.1038_nature00873
    DOI: 10.1038/nature00873
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