Inhibition of influenza A virus replication by short double-stranded oligodeoxynucleotides.
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.
Kwok
Terry
T
Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Helfer
Hanspeter
H
Alam
Mohammad Intakhab
MI
Heinrich
Jochen
J
Pavlovic
Jovan
J
Moelling
Karin
K
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D004247:DNA / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology*; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*
D009838:Oligodeoxyribonucleotides; D004247:DNA