Inhibition of influenza A virus replication by short double-stranded oligodeoxynucleotides |
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Authors: | Terry Kwok Hanspeter Helfer Mohammad Intakhab Alam Jochen Heinrich Jovan Pavlovic and Karin Moelling |
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Institution: | (1) Institute of Medical Virology, University of Zurich, Gloriastrasse 30/32, 8006 Zurich, Switzerland |
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Abstract: | Influenza A virus causes prevalent respiratory tract infections in humans. Small interfering RNA (siRNA) and antisense oligonucleotides
(asODNs) have been used previously for silencing the RNA genome of influenza virus. Here, we explored the use of partially
double-stranded oligodeoxynucleotides (dsODNs) to suppress the production of influenza A virus in cell cultures and animal
models. We were able to inhibit influenza A virus replication in cultured human lung cells as well as in the lungs of infected
C57BL/6 mice by treatment with dsODN 3-h post-infection. In about 20% of the cases (15/77) the titer was reduced by 10- to
100-fold and in 10% up to 1,000-fold. The antiviral effects of dsODNs were dose-dependent, sequence-dependent and comparable
to those of its antisense and siRNA analogues. Thus, dsODNs may be developed as an additional class of nucleic acids for the
inhibition of influenza virus replication. |
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