Suppression of RNA Interference by Adenovirus Virus-Associated RNA
| Autor: | Ning Xu, Ben Berkhout, P.C. Joost Haasnoot, Saideh Berenjian, Göran Akusjärvi, Gunnar Andersson |
|---|---|
| Přispěvatelé: | Medical Microbiology and Infection Prevention, AII - Amsterdam institute for Infection and Immunity |
| Rok vydání: | 2005 |
| Předmět: |
Ribonuclease III
Small interfering RNA Virus Integration Molecular Sequence Data Immunology Mutant Biology medicine.disease_cause Microbiology Cell Line eIF-2 Kinase RNA interference Virology medicine Humans Gene silencing RNA Small Interfering Base Sequence Adenoviruses Human fungi RNA Molecular biology Genome Replication and Regulation of Viral Gene Expression Adenoviridae Lytic cycle Insect Science Mutation biology.protein RNA Viral RNA Interference Dicer |
| Zdroj: | Journal of virology, 79(15), 9556-9565. American Society for Microbiology |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.79.15.9556-9565.2005 |
| Popis: | We show that human adenovirus inhibits RNA interference (RNAi) at late times of infection by suppressing the activity of two key enzyme systems involved, Dicer and RNA-induced silencing complex (RISC). To define the mechanisms by which adenovirus blocks RNAi, we used a panel of mutant adenoviruses defective in virus-associated (VA) RNA expression. The results show that the virus-associated RNAs, VA RNAI and VA RNAII, function as suppressors of RNAi by interfering with the activity of Dicer. The VA RNAs bind Dicer and function as competitive substrates squelching Dicer. Further, we show that VA RNAI and VA RNAII are processed by Dicer, both in vitro and during a lytic infection, and that the resulting short interfering RNAs (siRNAs) are incorporated into active RISC. Dicer cleaves the terminal stem of both VA RNAI and VA RNAII. However, whereas both strands of the VA RNAI-specific siRNA are incorporated into RISC, the 3′ strand of the VA RNAII-specific siRNA is selectively incorporated during a lytic infection. In summary, our work shows that adenovirus suppresses RNAi during a lytic infection and gives insight into the mechanisms of RNAi suppression by VA RNA. |
| Databáze: | OpenAIRE |
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