Complete Cure of Persistent Virus Infections by Antiviral siRNAs
| Autor: | Isabelle Pelletier, Aure Saulnier, Karine Labadie, Florence Colbère-Garapin |
|---|---|
| Přispěvatelé: | Virus Entérotropes et Stratégies Antivirales, Institut Pasteur [Paris] (IP), Pasteur Institute (DVPI and PTR), and the Ministère (MENESR), Institut Pasteur [Paris] |
| Rok vydání: | 2006 |
| Předmět: |
Small interfering RNA
Mutant Virus Replication medicine.disease_cause [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases RNA interference Chlorocebus aethiops MESH: RNA Small Interfering Drug Discovery MESH: Animals RNA Small Interfering 0303 health sciences poliovirus enterovirus Poliovirus 030302 biochemistry & molecular biology antiviral 3. Good health Titer MESH: RNA Viral RNA Viral Molecular Medicine RNA Interference MESH: Poliovirus MESH: Mutation MESH: RNA Interference interference Biology Transfection Virus Cell Line posttranscriptional gene silencing 03 medical and health sciences Genetics medicine Animals Humans Molecular Biology 030304 developmental biology Pharmacology persistent infection MESH: Humans MESH: Transfection MESH: Virus Replication Genetic Therapy chronic infection MESH: Cercopithecus aethiops Virology MESH: Cell Line Chronic infection RNAi siRNA Mutation MESH: Poliomyelitis Enterovirus MESH: Gene Therapy Poliomyelitis |
| Zdroj: | Molecular Therapy Molecular Therapy, 2006, 13 (1), pp.142-50. ⟨10.1016/j.ymthe.2005.07.697⟩ Molecular Therapy, Cell Press, 2006, 13 (1), pp.142-50. ⟨10.1016/j.ymthe.2005.07.697⟩ |
| ISSN: | 1525-0016 1525-0024 |
| DOI: | 10.1016/j.ymthe.2005.07.697 |
| Popis: | Small interfering RNAs (siRNAs) have been developed as antiviral agents for mammalian cells. The capacity of specific siRNAs to prevent virus infections has been demonstrated, and there is evidence that these new antiviral agents could have a partial therapeutic effect a few days after infection. We investigated the possibility of curing a persistent infection, several months after becoming established, using an in vitro model of persistent poliovirus (PV) infection in HEp-2 cells. Despite high virus titers and the presence of PV mutants, repeated treatment with a mixture of two siRNAs targeting both noncoding and coding regions, one of them in a highly conserved region, resulted in the complete cure of the majority of persistently infected cultures. No escape mutants emerged in treated cultures. The antiviral effect of specific siRNAs, consistent with a mechanism of RNA interference, correlated with a decrease in the amount of viral RNA, until its complete disappearance, resulting in cultures cured of virions and viral RNA. |
| Databáze: | OpenAIRE |
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