Inhibition of Influenza Virus Replication by DNA Aptamers Targeting a Cellular Component of Translation Initiation
| Autor: | Amelia Nieto, M. Elena Martín, M. Isabel Pérez-Morgado, Víctor M. González, Paloma Rodriguez |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
biology Aptamer viruses lcsh:RM1-950 aptamers Translation (biology) Transfection Virology Virus 03 medical and health sciences influenza virus replication lcsh:Therapeutics. Pharmacology 030104 developmental biology Eukaryotic translation Viral replication Drug Discovery biology.protein Molecular Medicine Original Article polyA-binding protein Translation initiation complex Polymerase |
| Zdroj: | Molecular Therapy. Nucleic Acids Molecular Therapy: Nucleic Acids, Vol 5, Iss C (2016) Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid |
| ISSN: | 2162-2531 |
| Popis: | The genetic diversity of the influenza virus hinders the use of broad spectrum antiviral drugs and favors the appearance of resistant strains. Single-stranded DNA aptamers represent an innovative approach with potential application as antiviral compounds. The mRNAs of influenza virus possess a 5'cap structure and a 3'poly(A) tail that makes them structurally indistinguishable from cellular mRNAs. However, selective translation of viral mRNAs occurs in infected cells through a discriminatory mechanism, whereby viral polymerase and NS1 interact with components of the translation initiation complex, such as the eIF4GI and PABP1 proteins. We have studied the potential of two specific aptamers that recognize PABP1 (ApPABP7 and ApPABP11) to act as anti-influenza drugs. Both aptamers reduce viral genome expression and the production of infective influenza virus particles. The interaction of viral polymerase with the eIF4GI translation initiation factor is hindered by transfection of infected cells with both PABP1 aptamers, and ApPABP11 also inhibits the association of NS1 with PABP1 and eIF4GI. These results indicate that aptamers targeting the host factors that interact with viral proteins may potentially have a broad therapeutic spectrum, reducing the appearance of escape mutants and resistant subtypes. |
| Databáze: | OpenAIRE |
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