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J Virol. Sep 1993; 67(9): 5139–5145.
PMCID: PMC237911

Genetically engineered foot-and-mouth disease viruses with poly(C) tracts of two nucleotides are virulent in mice.


To determine the role of the poly(C) tract found at the 5' end of the genome of foot-and-mouth disease virus, synthetic RNAs (in vitro transcripts) with poly(C) tracts of different lengths have been produced and evaluated. RNAs with poly(C) tracts of 35, 25, 16, 6, or 2 residues displayed similar specific infectivities in baby hamster kidney (BHK) cells. Viruses recovered from cells transfected with in vitro transcripts containing 6 to 35 Cs had properties similar to those of the wild-type virus in cell culture, and poly(C) tracts present in the synthetic RNA-derived viruses ranged from 75 to 140 bases in length. Viruses recovered from transcripts containing only two Cs showed very different properties. Specifically, viruses grew to much lower levels in cell culture and maintained a poly(C) tract of only two residues. The pool of viruses harvested from cells transfected with the synthetic C2 RNA also contained a small amount of a virus with a 42-base deletion in the region of the poly(C) tract, which appeared to have arisen by recombination. Taken together, these data suggest that recombination provides the mechanism of poly(C) elongation and that viruses with poly(C) tracts over 75 bases in length have a selective advantage in cell culture. Interestingly, all of the in vitro transcript-derived viruses [including viruses with poly(C) tracts of only two residues] were equally virulent in mice, indicating that poly(C) tract length has no effect on virulence in this animal model.

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Selected References

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  • Beck E, Strohmaier K. Subtyping of European foot-and-mouth disease virus strains by nucleotide sequence determination. J Virol. 1987 May;61(5):1621–1629. [PMC free article] [PubMed]
  • Black DN, Stephenson P, Rowlands DJ, Brown F. Sequence and location of the poly C tract in aphtho- and cardiovirus RNA. Nucleic Acids Res. 1979 Jun 11;6(7):2381–2390. [PMC free article] [PubMed]
  • Brakenhoff RH, Schoenmakers JG, Lubsen NH. Chimeric cDNA clones: a novel PCR artifact. Nucleic Acids Res. 1991 Apr 25;19(8):1949–1949. [PMC free article] [PubMed]
  • Brown F, Newman J, Stott J, Porter A, Frisby D, Newton C, Carey N, Fellner P. Poly(C) in animal viral RNAs. Nature. 1974 Sep 27;251(5473):342–344. [PubMed]
  • Chumakov KM, Agol VI. Poly(C) sequence is located near the 5'-end of encephalomyocarditis virus RNA. Biochem Biophys Res Commun. 1976 Jul 26;71(2):551–557. [PubMed]
  • Clarke BE, Brown AL, Currey KM, Newton SE, Rowlands DJ, Carroll AR. Potential secondary and tertiary structure in the genomic RNA of foot and mouth disease virus. Nucleic Acids Res. 1987 Sep 11;15(17):7067–7079. [PMC free article] [PubMed]
  • Costa Giomi MP, Gomes I, Tiraboschi B, Auge de Mello P, Bergmann IE, Scodeller EA, La Torre JL. Heterogeneity of the polyribocytidilic acid tract in aphthovirus: changes in the size of the poly(C) of viruses recovered from persistently infected cattle. Virology. 1988 Jan;162(1):58–64. [PubMed]
  • Duke GM, Osorio JE, Palmenberg AC. Attenuation of Mengo virus through genetic engineering of the 5' noncoding poly(C) tract. Nature. 1990 Feb 1;343(6257):474–476. [PubMed]
  • Duke GM, Palmenberg AC. Cloning and synthesis of infectious cardiovirus RNAs containing short, discrete poly(C) tracts. J Virol. 1989 Apr;63(4):1822–1826. [PMC free article] [PubMed]
  • Escarmís C, Toja M, Medina M, Domingo E. Modifications of the 5' untranslated region of foot-and-mouth disease virus after prolonged persistence in cell culture. Virus Res. 1992 Nov;26(2):113–125. [PubMed]
  • Grubman MJ, Baxt B, Bachrach HL. Foot-and-mouth disease virion RNA: studies on the relation between the length of its 3'-poly(A) segment and infectivity. Virology. 1979 Aug;97(1):22–31. [PubMed]
  • Harris TJ. Comparison of the nucleotide sequence at the 5' end of RNAs from nine aphthoviruses, including representatives of the Seven serotypes. J Virol. 1980 Dec;36(3):659–664. [PMC free article] [PubMed]
  • Harris TJ, Brown F. The location of the ploy(C) tract in the RNA of foot-and-mouth disease virus. J Gen Virol. 1976 Dec;33(3):493–501. [PubMed]
  • Harris TJ, Brown F. Biochemical analysis of a virulent and an avirulent strain of foot-and-mouth disease virus. J Gen Virol. 1977 Jan;34(1):87–105. [PubMed]
  • Higuchi RG, Ochman H. Production of single-stranded DNA templates by exonuclease digestion following the polymerase chain reaction. Nucleic Acids Res. 1989 Jul 25;17(14):5865–5865. [PMC free article] [PubMed]
  • Jang SK, Kräusslich HG, Nicklin MJ, Duke GM, Palmenberg AC, Wimmer E. A segment of the 5' nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation. J Virol. 1988 Aug;62(8):2636–2643. [PMC free article] [PubMed]
  • Kirkegaard K, Baltimore D. The mechanism of RNA recombination in poliovirus. Cell. 1986 Nov 7;47(3):433–443. [PubMed]
  • Klug J, Wolf M, Beato M. Creating chimeric molecules by PCR directed homologous DNA recombination. Nucleic Acids Res. 1991 May 25;19(10):2793–2793. [PMC free article] [PubMed]
  • Lerner CG, Inouye M. Low copy number plasmids for regulated low-level expression of cloned genes in Escherichia coli with blue/white insert screening capability. Nucleic Acids Res. 1990 Aug 11;18(15):4631–4631. [PMC free article] [PubMed]
  • Mateu MG, Martínez MA, Rocha E, Andreu D, Parejo J, Giralt E, Sobrino F, Domingo E. Implications of a quasispecies genome structure: effect of frequent, naturally occurring amino acid substitutions on the antigenicity of foot-and-mouth disease virus. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5883–5887. [PMC free article] [PubMed]
  • Milligan JF, Groebe DR, Witherell GW, Uhlenbeck OC. Oligoribonucleotide synthesis using T7 RNA polymerase and synthetic DNA templates. Nucleic Acids Res. 1987 Nov 11;15(21):8783–8798. [PMC free article] [PubMed]
  • Newton SE, Carroll AR, Campbell RO, Clarke BE, Rowlands DJ. The sequence of foot-and-mouth disease virus RNA to the 5' side of the poly(C) tract. Gene. 1985;40(2-3):331–336. [PubMed]
  • Perez-Bercoff R, Gander M. The genomic RNA of mengovirus. I. Location of the poly(C) tract. Virology. 1977 Jul 15;80(2):426–429. [PubMed]
  • Pilipenko EV, Blinov VM, Agol VI. Gross rearrangements within the 5'-untranslated region of the picornaviral genomes. Nucleic Acids Res. 1990 Jun 11;18(11):3371–3375. [PMC free article] [PubMed]
  • Porter A, Carey N, Fellner P. Presence of a large poly(rC) tract within the RNA of encephalomyocarditis virus. Nature. 1974 Apr 19;248(5450):675–678. [PubMed]
  • Robertson BH, Grubman MJ, Weddell GN, Moore DM, Welsh JD, Fischer T, Dowbenko DJ, Yansura DG, Small B, Kleid DG. Nucleotide and amino acid sequence coding for polypeptides of foot-and-mouth disease virus type A12. J Virol. 1985 Jun;54(3):651–660. [PMC free article] [PubMed]
  • Rowlands DJ, Harris TJ, Brown F. More precise location of the polycytidylic acid tract in foot and mouth disease virus RNA. J Virol. 1978 May;26(2):335–343. [PMC free article] [PubMed]
  • Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. [PubMed]
  • Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985 Dec 20;230(4732):1350–1354. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Vakharia VN, Devaney MA, Moore DM, Dunn JJ, Grubman MJ. Proteolytic processing of foot-and-mouth disease virus polyproteins expressed in a cell-free system from clone-derived transcripts. J Virol. 1987 Oct;61(10):3199–3207. [PMC free article] [PubMed]
  • van der Werf S, Bradley J, Wimmer E, Studier FW, Dunn JJ. Synthesis of infectious poliovirus RNA by purified T7 RNA polymerase. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2330–2334. [PMC free article] [PubMed]
  • Winship PR. An improved method for directly sequencing PCR amplified material using dimethyl sulphoxide. Nucleic Acids Res. 1989 Feb 11;17(3):1266–1266. [PMC free article] [PubMed]
  • Yanisch-Perron C, Vieira J, Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. [PubMed]
  • Zibert A, Maass G, Strebel K, Falk MM, Beck E. Infectious foot-and-mouth disease virus derived from a cloned full-length cDNA. J Virol. 1990 Jun;64(6):2467–2473. [PMC free article] [PubMed]

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