Key result
DNA aptamers targeting PABP1 (ApPABP7 and ApPABP11) reduced viral genome expression and the production of infective influenza virus particles in infected cells.
Why the study?
Do DNA aptamers targeting PABP1 reduce influenza virus replication in infected cells?
Do DNA aptamers targeting PABP1 reduce influenza virus replication in infected cells?
DNA aptamers targeting host translation initiation factors like PABP1 represent a potential broad-spectrum antiviral strategy against influenza by reducing viral replication.
May support PABP1 aptamers as antiviral candidates; leaves open in vivo efficacy and clinical translation for influenza.
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.
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Rodriguez et al. (2016) studied Influenza virus infection. DNA aptamers targeting PABP1 (ApPABP7 and ApPABP11) was evaluated on Viral genome expression and production of infective influenza virus particles. DNA aptamers targeting PABP1 (ApPABP7 and ApPABP11) reduced viral genome expression and the production of infective influenza virus particles in infected cells.
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