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Nucleic Acids Research, 1989, Vol. 17, No. 22 9341-9394
© 1989

MOLECULAR BIOLOGY

Antiviral activity and possible mechanisms of action of oligonucleotides-poly(L-lysine) conjugates targeted to vesicular stomatitis virus mRNA and genomic RNA

Geneviève Degols, Jean-paul Leonetti, Corinne Gagnor, Marc Lemaitre and Bernard Lebleu

Laboratoire de Biochimie des Proteines UA CNRS 1191 Université des Sciences et Techniques du Languedoc Place E. Bataillon, 34060 Montpellier cedex, France

Received June 30, 1989. Revised September 14, 1989. Accepted October 17, 1989.

Synthetic oligonucleotides (oligomers) complementary to vesicular stomatitis virus (VSV) N protein mRNA have specific antiviral properties at concentrations lower than 1 µM when they are covalently linked to poly(L-lysine) (PLL). Since it is generally postulated that antisense oligomers act at the translational level, oligomers with potential targets on VSV viral mRNA and/or genomic RNA have been tested here. In vitro translation experiments in reticulocyte lysates, in vitro transcription experiments with permeabilized viruses, measurement of viral RNA transcription and accumulation in VSV infected cells, and antiviral experiments demonstrate in our model that antisense oligomers probably also act at other levels. Difficulties in the choice of the most effective antisense oligomer targets are also discussed.


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