• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
J Virol. Nov 1994; 68(11): 7426–7432.
PMCID: PMC237185

Specific inhibition of aphthovirus infection by RNAs transcribed from both the 5' and the 3' noncoding regions.

Abstract

RNA molecules containing the 3' terminal region of foot-and-mouth disease virus (FMDV) RNA in both antisense and sense orientations were able to inhibit viral FMDV translation and infective particle formation in BHK-21 cells following comicroinjection or cotransfection with infectious viral RNA. Antisense, but not sense, transcripts from the 5' noncoding region including the proximal element of the internal ribosome entry site and the two functional initiation AUGs were also inhibitory, both in in vitro translation and in vivo in comicroinjected or cotransfected BHK-21 cells. This effect was not observed with nonrelated RNA transcripts from lambda phage. The inhibitions found were permanent, sequence specific, and dose dependent; an inverse correlation between the length of the transcript and the extent of the antiviral effect was seen. In all cases, the extent of inhibition increased when viral RNAs and transcripts were allowed to reanneal before transfection, concomitant with a decrease in the doses required. The antiviral effect was specific for FMDV, since transcripts failed to inhibit infective particle formation by other picornavirus, such as encephalomyocarditis virus. These results indicate that the ability of RNA transcripts to inhibit viral multiplication depends on their efficient hybridization with target regions on the viral genome. Furthermore, cells transfected with the 5'1as transcript, which is complementary to the 5' noncoding region, showed a significant reduction of plaque-forming ability during the course of a natural infection. RNA 5'1as was able to inhibit FMDV RNA translation in vitro, suggesting that the inhibitions observed are mediated by a blockage of the viral translation initiation. Conversely, hybridization of short sequences of both sense and antisense transcripts from the 3' end induces distortion of predicted highly ordered structural motifs, which could be required for the synthesis of negative-stranded viral RNA, and correlates with inhibition of viral propagation.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Agrawal S. Antisense oligonucleotides as antiviral agents. Trends Biotechnol. 1992 May;10(5):152–158. [PubMed]
  • Arlinghaus RB, Polatnick J. The isolation of two enzyme-ribonucleic acid complexes involved in the synthesis of foot-and-mouth disease virus ribonucleic acid. Proc Natl Acad Sci U S A. 1969 Mar;62(3):821–828. [PMC free article] [PubMed]
  • Beck E, Forss S, Strebel K, Cattaneo R, Feil G. Structure of the FMDV translation initiation site and of the structural proteins. Nucleic Acids Res. 1983 Nov 25;11(22):7873–7885. [PMC free article] [PubMed]
  • Belsham GJ, Bostock CJ. Studies on the infectivity of foot-and-mouth disease virus RNA using microinjection. J Gen Virol. 1988 Feb;69(Pt 2):265–274. [PubMed]
  • Belsham GJ, Brangwyn JK. A region of the 5' noncoding region of foot-and-mouth disease virus RNA directs efficient internal initiation of protein synthesis within cells: involvement with the role of L protease in translational control. J Virol. 1990 Nov;64(11):5389–5395. [PMC free article] [PubMed]
  • Brown F. New approaches to vaccination against foot-and-mouth disease. Vaccine. 1992;10(14):1022–1026. [PubMed]
  • Cameron FH, Jennings PA. Inhibition of gene expression by a short sense fragment. Nucleic Acids Res. 1991 Feb 11;19(3):469–475. [PMC free article] [PubMed]
  • Cohen JS. Antisense oligodeoxynucleotides as antiviral agents. Antiviral Res. 1991 Sep;16(2):121–133. [PubMed]
  • Cole CN, Baltimore D. Defective interfering particles of poliovirus. 3. Interference and enrichment. J Mol Biol. 1973 May 25;76(3):345–361. [PubMed]
  • Cole CN, Baltimore D. Defective interfering particles of poliovirus. IV. Mechanisms of enrichment. J Virol. 1973 Dec;12(6):1414–1426. [PMC free article] [PubMed]
  • Collis PS, O'Donnell BJ, Barton DJ, Rogers JA, Flanegan JB. Replication of poliovirus RNA and subgenomic RNA transcripts in transfected cells. J Virol. 1992 Nov;66(11):6480–6488. [PMC free article] [PubMed]
  • Degols G, Leonetti JP, Gagnor C, Lemaitre M, Lebleu B. Antiviral activity and possible mechanisms of action of oligonucleotides-poly(L-lysine) conjugates targeted to vesicular stomatitis virus mRNA and genomic RNA. Nucleic Acids Res. 1989 Nov 25;17(22):9341–9350. [PMC free article] [PubMed]
  • Domingo E, Dávila M, Ortín J. Nucleotide sequence heterogeneity of the RNA from a natural population of foot-and-mouth-disease virus. Gene. 1980 Nov;11(3-4):333–346. [PubMed]
  • Graessmann M, Graessmann A. The biological activity of early SV40 antisense RNA and DNA molecules. Curr Top Microbiol Immunol. 1989;144:97–103. [PubMed]
  • Gutiérrez A, Rodríguez A, Pintado B, Sobrino F. Transient inhibition of foot-and-mouth disease virus infection of BHK-21 cells by antisense oligonucleotides directed against the second functional initiator AUG. Antiviral Res. 1993 Sep;22(1):1–13. [PubMed]
  • Hélène C, Toulmé JJ. Specific regulation of gene expression by antisense, sense and antigene nucleic acids. Biochim Biophys Acta. 1990 Jun 21;1049(2):99–125. [PubMed]
  • Iizuka N, Kuge S, Nomoto A. Complete nucleotide sequence of the genome of coxsackievirus B1. Virology. 1987 Jan;156(1):64–73. [PubMed]
  • Jackson RJ, Howell MT, Kaminski A. The novel mechanism of initiation of picornavirus RNA translation. Trends Biochem Sci. 1990 Dec;15(12):477–483. [PubMed]
  • Jacobson SJ, Konings DA, Sarnow P. Biochemical and genetic evidence for a pseudoknot structure at the 3' terminus of the poliovirus RNA genome and its role in viral RNA amplification. J Virol. 1993 Jun;67(6):2961–2971. [PMC free article] [PubMed]
  • Joshi S, Van Brunschot A, Asad S, van der Elst I, Read SE, Bernstein A. Inhibition of human immunodeficiency virus type 1 multiplication by antisense and sense RNA expression. J Virol. 1991 Oct;65(10):5524–5530. [PMC free article] [PubMed]
  • Kaplan G, Racaniello VR. Construction and characterization of poliovirus subgenomic replicons. J Virol. 1988 May;62(5):1687–1696. [PMC free article] [PubMed]
  • Kim SK, Wold BJ. Stable reduction of thymidine kinase activity in cells expressing high levels of anti-sense RNA. Cell. 1985 Aug;42(1):129–138. [PubMed]
  • Konings DA, Mattaj IW. Mutant U2 snRNAs of Xenopus which can form an altered higher order RNA structure are unable to enter the nucleus. Exp Cell Res. 1987 Oct;172(2):329–339. [PubMed]
  • Kühn R, Luz N, Beck E. Functional analysis of the internal translation initiation site of foot-and-mouth disease virus. J Virol. 1990 Oct;64(10):4625–4631. [PMC free article] [PubMed]
  • Martinez MA, Carrillo C, Plana J, Mascarella R, Bergada J, Palma EL, Domingo E, Sobrino F. Genetic and immunogenic variations among closely related isolates of foot-and-mouth disease virus. Gene. 1988;62(1):75–84. [PubMed]
  • Martínez-Salas E, Sáiz JC, Dávila M, Belsham GJ, Domingo E. A single nucleotide substitution in the internal ribosome entry site of foot-and-mouth disease virus leads to enhanced cap-independent translation in vivo. J Virol. 1993 Jul;67(7):3748–3755. [PMC free article] [PubMed]
  • Mateu MG, Rocha E, Vicente O, Vayreda F, Navalpotro C, Andreu D, Pedroso E, Giralt E, Enjuanes L, Domingo E. Reactivity with monoclonal antibodies of viruses from an episode of foot-and-mouth disease. Virus Res. 1987 Sep;8(3):261–274. [PubMed]
  • Pilipenko EV, Blinov VM, Chernov BK, Dmitrieva TM, Agol VI. Conservation of the secondary structure elements of the 5'-untranslated region of cardio- and aphthovirus RNAs. Nucleic Acids Res. 1989 Jul 25;17(14):5701–5711. [PMC free article] [PubMed]
  • Ricker RD, Kaji A. Studies on antisense inhibition of translation in vitro. Anomalies and re-evaluation. FEBS Lett. 1992 Sep 14;309(3):363–370. [PubMed]
  • Sangar DV. The replication of picornaviruses. J Gen Virol. 1979 Oct;45(1):1–13. [PubMed]
  • Sczakiel G, Pawlita M. Inhibition of human immunodeficiency virus type 1 replication in human T cells stably expressing antisense RNA. J Virol. 1991 Jan;65(1):468–472. [PMC free article] [PubMed]
  • Shih DS, Park IW, Evans CL, Jaynes JM, Palmenberg AC. Effects of cDNA hybridization on translation of encephalomyocarditis virus RNA. J Virol. 1987 Jun;61(6):2033–2037. [PMC free article] [PubMed]
  • Strebel K, Beck E, Strohmaier K, Schaller H. Characterization of foot-and-mouth disease virus gene products with antisera against bacterially synthesized fusion proteins. J Virol. 1986 Mar;57(3):983–991. [PMC free article] [PubMed]
  • Sullenger BA, Gallardo HF, Ungers GE, Gilboa E. Analysis of trans-acting response decoy RNA-mediated inhibition of human immunodeficiency virus type 1 transactivation. J Virol. 1991 Dec;65(12):6811–6816. [PMC free article] [PubMed]
  • Sullenger BA, Lee TC, Smith CA, Ungers GE, Gilboa E. Expression of chimeric tRNA-driven antisense transcripts renders NIH 3T3 cells highly resistant to Moloney murine leukemia virus replication. Mol Cell Biol. 1990 Dec;10(12):6512–6523. [PMC free article] [PubMed]
  • Takayama KM, Inouye M. Antisense RNA. Crit Rev Biochem Mol Biol. 1990;25(3):155–184. [PubMed]
  • Zuker M, Stiegler P. Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Res. 1981 Jan 10;9(1):133–148. [PMC free article] [PubMed]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...