This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.00557-07v1 81/21/11669    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vagnozzi, A. Articles by Rieder, E. Search for Related Content PubMed PubMed Citation Articles by Vagnozzi, A. Articles by Rieder, E.

 Previous Article  |  Next Article 

Journal of Virology, November 2007, p. 11669-11680, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.00557-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Inhibition of Foot-and-Mouth Disease Virus Infections in Cell Cultures with Antisense Morpholino Oligomers

Foreign Animal Disease Research Unit, United States Department of Agriculture, Agricultural Research Service, Plum Island Animal Disease Center, Greenport, New York 11944,¹ AVI BioPharma Inc., Corvallis, Oregon 97333²

Received 16 March 2007/ Accepted 24 August 2007

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed ungulates that can lead to severe losses in the livestock production and export industries. Although vaccines have been extensively used to control FMD, there is no antiviral therapy available to treat ongoing infections with FMD virus (FMDV). Six peptide-conjugated morpholino oligomers (PPMOs) with sequences complementary to various 21-nucleotide segments of the 5' and 3' untranslated regions (UTRs) of the FMDV genome (strain A₂₄ Cruzeiro/Brazil/1955 [A₂₄Cru]) were evaluated in cell cultures. Three of the PPMOs, targeting domain 5 of the internal ribosome entry site (5D PPMO), and the two translation start codon regions (AUG1 and AUG2 PPMOs), showed high levels of anti-FMDV activity. A dose-dependent and sequence-specific reduction in viral titers of greater than 5 log₁₀, with a concomitant reduction of viral protein and RNA expression, was achieved at low micromolar concentrations. Under identical conditions, three other PPMOs targeting the 5'-terminal region of the genome, the cis-acting replication element in the 5' UTR, and the 3' "ab" stem-loop showed less dramatic titer reductions of 1.5 log₁₀ to 2 log₁₀. Treatment with 5D PPMO reduced the titers of FMDV strains representing five different serotypes by 2 log₁₀ to 4 log₁₀ compared to those of the controls. A₂₄Cru-infected BHK-21 cells treated repeatedly with 5D or AUG2 PPMO generated resistant viruses for which phenotypic and genotypic properties were defined. Notably, three passages with low concentrations of the AUG1 PPMO extinguished all traces of detectable virus. The results indicate that PPMOs have potential for treating FMDV infections and that they also represent useful tools for studying picornaviral translation and evolution.

Published ahead of print on 29 August 2007.

This article has been cited by other articles:

• Stone, J. K., Rijnbrand, R., Stein, D. A., Ma, Y., Yang, Y., Iversen, P. L., Andino, R. (2008). A Morpholino Oligomer Targeting Highly Conserved Internal Ribosome Entry Site Sequence Is Able To Inhibit Multiple Species of Picornavirus. Antimicrob. Agents Chemother. 52: 1970-1981 [Abstract] [Full Text]