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. 1986 Feb;57(2):638–646. doi: 10.1128/jvi.57.2.638-646.1986

Guanidine-selected mutants of poliovirus: mapping of point mutations to polypeptide 2C.

S E Pincus, D C Diamond, E A Emini, E Wimmer
PMCID: PMC252779  PMID: 3003395

Abstract

Sequence analysis of the genomic RNA of interstrain guanidine-resistant and antibody-resistant variant recombinants of poliovirus type 1 mapped the resistance of mutants capable of growth in 2.0 mM guanidine hydrochloride to a region located 3' of nucleotide 4444. This region of the viral genome specifies the nonstructural protein 2C. The sequence of genomic RNA encoding 2C from six independently isolated mutants resistant to 2.0 mM guanidine was determined. All six isolates contained a mutation in 2C at the same position in all cases, resulting in two types of amino acid changes. Dependent mutants were examined and found to contain two amino acid changes each within 2C. Mutants resistant to 0.53 mM guanidine were isolated and found to lack the mutations seen in variants resistant to 2.0 mM guanidine. A comparison of the amino acid sequences of the 2C proteins of poliovirus, foot-and-mouth disease virus, rhinovirus types 2 and 14, and encephalomyocarditis virus revealed a strong homology over regions totaling 115 residues. All of the mutations observed in guanidine-selected mutants were contained within this region. The amino acid region containing the mutations observed in poliovirus mutants resistant to 2.0 mM guanidine was compared with the homologous region in the other picornaviruses; a strong correlation was found between the amino acid present at this position and the sensitivity of the virus to 2.0 mM guanidine.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson-Sillman K., Bartal S., Tershak D. R. Guanidine-resistant poliovirus mutants produce modified 37-kilodalton proteins. J Virol. 1984 Jun;50(3):922–928. doi: 10.1128/jvi.50.3.922-928.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Argos P., Kamer G., Nicklin M. J., Wimmer E. Similarity in gene organization and homology between proteins of animal picornaviruses and a plant comovirus suggest common ancestry of these virus families. Nucleic Acids Res. 1984 Sep 25;12(18):7251–7267. doi: 10.1093/nar/12.18.7251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Biggin M. D., Gibson T. J., Hong G. F. Buffer gradient gels and 35S label as an aid to rapid DNA sequence determination. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3963–3965. doi: 10.1073/pnas.80.13.3963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Butterworth B. E., Shimshick E. J., Yin F. H. Association of the polioviral RNA polymerase complex with phospholipid membranes. J Virol. 1976 Aug;19(2):457–466. doi: 10.1128/jvi.19.2.457-466.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. CROWTHER D., MELNICK J. L. Studies of the inhibitory action of guanidine on poliovirus multiplication in cell cultures. Virology. 1961 Sep;15:65–74. doi: 10.1016/0042-6822(61)90078-2. [DOI] [PubMed] [Google Scholar]
  6. Caliguiri L. A., Tamm I. Action of guanidine on the replication of poliovirus RNA. Virology. 1968 Jul;35(3):408–417. doi: 10.1016/0042-6822(68)90219-5. [DOI] [PubMed] [Google Scholar]
  7. Caliguiri L. A., Tamm I. The role of cytoplasmic membranes in poliovirus biosynthesis. Virology. 1970 Sep;42(1):100–111. doi: 10.1016/0042-6822(70)90242-4. [DOI] [PubMed] [Google Scholar]
  8. Carroll A. R., Rowlands D. J., Clarke B. E. The complete nucleotide sequence of the RNA coding for the primary translation product of foot and mouth disease virus. Nucleic Acids Res. 1984 Mar 12;12(5):2461–2472. doi: 10.1093/nar/12.5.2461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cole C. N., Baltimore D. Defective interfering particles of poliovirus. II. Nature of the defect. J Mol Biol. 1973 May 25;76(3):325–343. doi: 10.1016/0022-2836(73)90508-1. [DOI] [PubMed] [Google Scholar]
  10. Cooper P. D., Wentworth B. B., McCahon D. Guanidine inhibition of poliovirus: a dependence of viral RNA synthesis on the configuration of structural protein. Virology. 1970 Mar;40(3):480–493. doi: 10.1016/0042-6822(70)90191-1. [DOI] [PubMed] [Google Scholar]
  11. Dawson W. O. Guanidine inhibits tobacco mosaic virus RNA synthesis at two stages. Intervirology. 1975;6(2):83–89. doi: 10.1159/000149459. [DOI] [PubMed] [Google Scholar]
  12. Diamond D. C., Jameson B. A., Bonin J., Kohara M., Abe S., Itoh H., Komatsu T., Arita M., Kuge S., Nomoto A. Antigenic variation and resistance to neutralization in poliovirus type 1. Science. 1985 Sep 13;229(4718):1090–1093. doi: 10.1126/science.2412292. [DOI] [PubMed] [Google Scholar]
  13. EGGERS H. J., TAMM I. COXSACKIE A9 VIRUS: MUTATION FROM DRUG DEPENDENCE TO DRUG INDEPENDENCE. Science. 1965 Apr 2;148(3666):97–98. doi: 10.1126/science.148.3666.97. [DOI] [PubMed] [Google Scholar]
  14. Emini E. A., Leibowitz J., Diamond D. C., Bonin J., Wimmer E. Recombinants of Mahoney and Sabin strain poliovirus type 1: analysis of in vitro phenotypic markers and evidence that resistance to guanidine maps in the nonstructural proteins. Virology. 1984 Aug;137(1):74–85. doi: 10.1016/0042-6822(84)90010-2. [DOI] [PubMed] [Google Scholar]
  15. Forss S., Strebel K., Beck E., Schaller H. Nucleotide sequence and genome organization of foot-and-mouth disease virus. Nucleic Acids Res. 1984 Aug 24;12(16):6587–6601. doi: 10.1093/nar/12.16.6587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Franssen H., Leunissen J., Goldbach R., Lomonossoff G., Zimmern D. Homologous sequences in non-structural proteins from cowpea mosaic virus and picornaviruses. EMBO J. 1984 Apr;3(4):855–861. doi: 10.1002/j.1460-2075.1984.tb01896.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Friedman R. M. Basis for variable response of arboviruses to guanidine treatment. J Virol. 1970 Nov;6(5):628–636. doi: 10.1128/jvi.6.5.628-636.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Holland J. J., Kohne D., Doyle M. V. Analysis of virus replication in ageing human fibroblast cultures. Nature. 1973 Oct 12;245(5424):316–319. doi: 10.1038/245316a0. [DOI] [PubMed] [Google Scholar]
  19. Holland J., Spindler K., Horodyski F., Grabau E., Nichol S., VandePol S. Rapid evolution of RNA genomes. Science. 1982 Mar 26;215(4540):1577–1585. doi: 10.1126/science.7041255. [DOI] [PubMed] [Google Scholar]
  20. Huang A. S., Balitmore D. Initiation of polyribosome formation in poliovirus-infected HeLa cells. J Mol Biol. 1970 Feb 14;47(3):275–291. doi: 10.1016/0022-2836(70)90302-5. [DOI] [PubMed] [Google Scholar]
  21. Jacobson M. F., Baltimore D. Morphogenesis of poliovirus. I. Association of the viral RNA with coat protein. J Mol Biol. 1968 Apr 28;33(2):369–378. doi: 10.1016/0022-2836(68)90195-2. [DOI] [PubMed] [Google Scholar]
  22. Kitamura N., Semler B. L., Rothberg P. G., Larsen G. R., Adler C. J., Dorner A. J., Emini E. A., Hanecak R., Lee J. J., van der Werf S. Primary structure, gene organization and polypeptide expression of poliovirus RNA. Nature. 1981 Jun 18;291(5816):547–553. doi: 10.1038/291547a0. [DOI] [PubMed] [Google Scholar]
  23. LEDINKO N. Genetic recombination with poliovirus type 1. Studies of crosses between a normal horse serum-resistant mutant and several guanidine-resistant mutants of the same strain. Virology. 1963 May;20:107–119. doi: 10.1016/0042-6822(63)90145-4. [DOI] [PubMed] [Google Scholar]
  24. LODDO B., FERRARI W., BROTZU G., SPANEDDA A. In vitro inhibition of infectivity of polio viruses by guanidine. Nature. 1962 Jan 6;193:97–98. doi: 10.1038/193097a0. [DOI] [PubMed] [Google Scholar]
  25. LODDO B., MUNTONI S., SPANEDDA A., BROTZU G., FERRARI W. Guanidine conditioned infectivity of ribonucleic acid extracted from a strain of guanidine-dependent polio-1-virus. Nature. 1963 Jan 19;197:315–315. doi: 10.1038/197315a0. [DOI] [PubMed] [Google Scholar]
  26. Lake J. R., Priston A. J., Slade W. R. A genetic recombination map of foot-and-mouth disease virus. J Gen Virol. 1975 Jun;27(3):355–367. doi: 10.1099/0022-1317-27-3-355. [DOI] [PubMed] [Google Scholar]
  27. Lee Y. S., Yajima Y., Nonoyama M. Mechanism of infection by Epstein-Barr virus. II. Comparison of viral DNA from HR-1 and superinfected Raji cells by restriction enzymes. Virology. 1977 Aug;81(1):17–24. doi: 10.1016/0042-6822(77)90054-x. [DOI] [PubMed] [Google Scholar]
  28. McCahon D., Slade W. R., Priston R. A., Lake J. R. An extended genetic recombination map for foot-and-mouth diseases virus. J Gen Virol. 1977 Jun;35(3):555–565. doi: 10.1099/0022-1317-35-3-555. [DOI] [PubMed] [Google Scholar]
  29. Noble J., Levintow L. Dynamics of poliovirus-specific RNA synthesis and the effects of inhibitors of virus replication. Virology. 1970 Mar;40(3):634–642. doi: 10.1016/0042-6822(70)90208-4. [DOI] [PubMed] [Google Scholar]
  30. Nomoto A., Jacobson A., Lee Y. F., Dunn J., Wimmer E. Defective interfering particles of poliovirus: mapping of the deletion and evidence that the deletions in the genomes of DI(1), (2) and (3) are located in the same region. J Mol Biol. 1979 Feb 25;128(2):179–196. doi: 10.1016/0022-2836(79)90125-6. [DOI] [PubMed] [Google Scholar]
  31. Nomoto A., Omata T., Toyoda H., Kuge S., Horie H., Kataoka Y., Genba Y., Nakano Y., Imura N. Complete nucleotide sequence of the attenuated poliovirus Sabin 1 strain genome. Proc Natl Acad Sci U S A. 1982 Oct;79(19):5793–5797. doi: 10.1073/pnas.79.19.5793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. PRINGLE C. R. INHIBITION OF MULTIPLICATION OF FOOT-AND-MOUTH DISEASE VIRUS BY GUANIDINE HYDROCHLORIDE. Nature. 1964 Dec 5;204:1012–1013. doi: 10.1038/2041012a0. [DOI] [PubMed] [Google Scholar]
  33. Penman S., Summers D. Effects on host cell metabolism following synchronous infection with poliovirus. Virology. 1965 Dec;27(4):614–620. doi: 10.1016/0042-6822(65)90187-x. [DOI] [PubMed] [Google Scholar]
  34. RIGHTSEL W. A., DICE J. R., McALPINE R. J., TIMM E. A., McLEAN I. W., Jr, DIXON G. J., SCHABEL F. M., Jr Antiviral effect of guanidine. Science. 1961 Aug 25;134(3478):558–559. doi: 10.1126/science.134.3478.558. [DOI] [PubMed] [Google Scholar]
  35. Racaniello V. R., Baltimore D. Molecular cloning of poliovirus cDNA and determination of the complete nucleotide sequence of the viral genome. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4887–4891. doi: 10.1073/pnas.78.8.4887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Robertson B. H., Grubman M. J., Weddell G. N., Moore D. M., Welsh J. D., Fischer T., Dowbenko D. J., Yansura D. G., Small B., Kleid D. G. Nucleotide and amino acid sequence coding for polypeptides of foot-and-mouth disease virus type A12. J Virol. 1985 Jun;54(3):651–660. doi: 10.1128/jvi.54.3.651-660.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rueckert R. R., Wimmer E. Systematic nomenclature of picornavirus proteins. J Virol. 1984 Jun;50(3):957–959. doi: 10.1128/jvi.50.3.957-959.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Saunders K., King A. M. Guanidine-resistant mutants of aphthovirus induce the synthesis of an altered nonstructural polypeptide, P34. J Virol. 1982 May;42(2):389–394. doi: 10.1128/jvi.42.2.389-394.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sergiescu D., Horodniceanu F., Aubert-Combiescu A. The use of inhibitors in the study of picornavirus genetics. Prog Med Virol. 1972;14:123–199. [PubMed] [Google Scholar]
  40. Skern T., Sommergruber W., Blaas D., Gruendler P., Fraundorfer F., Pieler C., Fogy I., Kuechler E. Human rhinovirus 2: complete nucleotide sequence and proteolytic processing signals in the capsid protein region. Nucleic Acids Res. 1985 Mar 25;13(6):2111–2126. doi: 10.1093/nar/13.6.2111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Stanway G., Hughes P. J., Mountford R. C., Minor P. D., Almond J. W. The complete nucleotide sequence of a common cold virus: human rhinovirus 14. Nucleic Acids Res. 1984 Oct 25;12(20):7859–7875. doi: 10.1093/nar/12.20.7859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. TAMM I., EGGERS H. J. SPECIFIC INHIBITION OF REPLICATION OF ANIMAL VIRUSES. Science. 1963 Oct 4;142(3588):24–33. doi: 10.1126/science.142.3588.24. [DOI] [PubMed] [Google Scholar]
  43. Takegami T., Semler B. L., Anderson C. W., Wimmer E. Membrane fractions active in poliovirus RNA replication contain VPg precursor polypeptides. Virology. 1983 Jul 15;128(1):33–47. doi: 10.1016/0042-6822(83)90316-1. [DOI] [PubMed] [Google Scholar]
  44. Tershak D. R. Association of poliovirus proteins with the endoplasmic reticulum. J Virol. 1984 Dec;52(3):777–783. doi: 10.1128/jvi.52.3.777-783.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Tershak D. R. Inhibition of poliovirus polymerase by guanidine in vitro. J Virol. 1982 Jan;41(1):313–318. doi: 10.1128/jvi.41.1.313-318.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Tolskaya E. A., Romanova L. A., Kolesnikova M. S., Agol V. I. Intertypic recombination in poliovirus: genetic and biochemical studies. Virology. 1983 Jan 15;124(1):121–132. doi: 10.1016/0042-6822(83)90295-7. [DOI] [PubMed] [Google Scholar]
  47. Toyoda H., Kohara M., Kataoka Y., Suganuma T., Omata T., Imura N., Nomoto A. Complete nucleotide sequences of all three poliovirus serotype genomes. Implication for genetic relationship, gene function and antigenic determinants. J Mol Biol. 1984 Apr 25;174(4):561–585. doi: 10.1016/0022-2836(84)90084-6. [DOI] [PubMed] [Google Scholar]
  48. Varma J. P. Inhibition of tobacco necrosis virus by guanidine carbonate. Virology. 1968 Oct;36(2):305–308. doi: 10.1016/0042-6822(68)90149-9. [DOI] [PubMed] [Google Scholar]
  49. Yin F. H. Involvement of viral procapsid in the RNA synthesis and maturation of poliovirus. Virology. 1977 Oct 15;82(2):299–307. doi: 10.1016/0042-6822(77)90005-8. [DOI] [PubMed] [Google Scholar]

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