Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6896
pubmed:dateCreated
2002-7-25
pubmed:abstractText
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 mechanism. Animal cells also possess this machinery but its specific function is unclear. 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.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0028-0836
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
418
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
430-4
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12087357-Animals, pubmed-meshheading:12087357-Antiviral Agents, pubmed-meshheading:12087357-Base Sequence, pubmed-meshheading:12087357-Cell Line, pubmed-meshheading:12087357-Fibroblasts, pubmed-meshheading:12087357-Flow Cytometry, pubmed-meshheading:12087357-Fluorescent Antibody Technique, pubmed-meshheading:12087357-Gene Silencing, pubmed-meshheading:12087357-Genome, Viral, pubmed-meshheading:12087357-HeLa Cells, pubmed-meshheading:12087357-Humans, pubmed-meshheading:12087357-Interferons, pubmed-meshheading:12087357-Mice, pubmed-meshheading:12087357-Mutation, pubmed-meshheading:12087357-Poliovirus, pubmed-meshheading:12087357-RNA, Double-Stranded, pubmed-meshheading:12087357-RNA, Small Interfering, pubmed-meshheading:12087357-RNA, Untranslated, pubmed-meshheading:12087357-Virus Replication
pubmed:year
2002
pubmed:articleTitle
Short interfering RNA confers intracellular antiviral immunity in human cells.
pubmed:affiliation
Department of Microbiology and Immunology, Box 0414 and Program in Neuroscience, University of California, San Francisco, California 94143-0414, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.