Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1982 Sep;79(17):5220–5224. doi: 10.1073/pnas.79.17.5220

Viroids and prions.

T O Diener, M P McKinley, S B Prusiner
PMCID: PMC346867  PMID: 6813855

Abstract

Viroids are small "naked" infectious RNA molecules that are pathogens of higher plants. The potato spindle tuber viroid (PSTV) is composed of a covalently closed circular RNA molecule containing 359 ribonucleotides. The properties of PSTV were compared with those of the scrapie agent, which causes a degenerative neurological disease in animals. PSTV was inactivated by ribonuclease digestion, psoralen photoadduct formation, Zn2+ -catalyzed hydrolysis, and chemical modification with NH2OH. The scrapie agent resisted inactivation by these procedures, which modify nucleic acids. The scrapie agent was inactivated by proteinase K and trypsin digestion, chemical modification with diethylpyrocarbonate, and by exposure to phenol, NaDodSO4, KSCN, or urea. PSTV resisted inactivation by these procedures, which modify proteins. Earlier evidence suggested that the scrapie agent is smaller than PSTV. Its small size seems to preclude the presence of a genome coding for the protein(s) of a putative capsid. The properties of the scrapie agent distinguish it from both viroids and viruses and have prompted the introduction of the term "prion" to denote a small proteinaceous infectious particle that resists inactivation by procedures that modify nucleic acids.

Full text

PDF
5220

Selected References

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

  1. Alper T., Cramp W. A., Haig D. A., Clarke M. C. Does the agent of scrapie replicate without nucleic acid? Nature. 1967 May 20;214(5090):764–766. doi: 10.1038/214764a0. [DOI] [PubMed] [Google Scholar]
  2. Alper T., Haig D. A., Clarke M. C. The exceptionally small size of the scrapie agent. Biochem Biophys Res Commun. 1966 Feb 3;22(3):278–284. doi: 10.1016/0006-291x(66)90478-5. [DOI] [PubMed] [Google Scholar]
  3. Butzow J. J., Eichhorn G. L. Different susceptibility of DNA and RNA to cleavage by metal ions. Nature. 1975 Mar 27;254(5498):358–359. doi: 10.1038/254358a0. [DOI] [PubMed] [Google Scholar]
  4. Butzow J. J., Eichhorn G. L. Interactions of metal ions with polynucleotides and related compounds. IV. Degradation of polyribonucleotides by zinc and other divalent metal ions. Biopolymers. 1965;3(1):95–107. doi: 10.1002/bip.360030110. [DOI] [PubMed] [Google Scholar]
  5. Diener T. O. Is the scrapie agent a viroid? Nat New Biol. 1972 Feb 16;235(59):218–219. doi: 10.1038/newbio235218a0. [DOI] [PubMed] [Google Scholar]
  6. Diener T. O. Potato spindle tuber "virus". IV. A replicating, low molecular weight RNA. Virology. 1971 Aug;45(2):411–428. doi: 10.1016/0042-6822(71)90342-4. [DOI] [PubMed] [Google Scholar]
  7. Diener T. O. Potato spindle tuber virus: a plant virus with properties of a free nucleic acid. 3. Subcellular location of PSTV-RNA and the question of whether virions exist in extracts or in situ. Virology. 1971 Jan;43(1):75–89. doi: 10.1016/0042-6822(71)90226-1. [DOI] [PubMed] [Google Scholar]
  8. Diener T. O., Raymer W. B. Potato spindle tuber virus: a plant virus with properties of a free nucleic acid. II. Characterization and partial purification. Virology. 1969 Mar;37(3):351–366. doi: 10.1016/0042-6822(69)90219-0. [DOI] [PubMed] [Google Scholar]
  9. Diener T. O., Schneider I. R., Smith D. R. Potato spindle tuber viroid. XI. A comparison of the ultraviolet light sensitivities of PSTV, tobacco ringspot virus, and its satellite. Virology. 1974 Feb;57(2):577–581. doi: 10.1016/0042-6822(74)90198-6. [DOI] [PubMed] [Google Scholar]
  10. Ehrenberg L., Fedorcsak I., Solymosy F. Diethyl pyrocarbonate in nucleic acid research. Prog Nucleic Acid Res Mol Biol. 1976;16:189–262. doi: 10.1016/s0079-6603(08)60758-8. [DOI] [PubMed] [Google Scholar]
  11. Gross H. J., Domdey H., Lossow C., Jank P., Raba M., Alberty H., Sänger H. L. Nucleotide sequence and secondary structure of potato spindle tuber viroid. Nature. 1978 May 18;273(5659):203–208. doi: 10.1038/273203a0. [DOI] [PubMed] [Google Scholar]
  12. Gross H. J., Riesner D. Viroids: a class of subviral pathogens. Angew Chem Int Ed Engl. 1980;19(4):231–243. doi: 10.1002/anie.198002313. [DOI] [PubMed] [Google Scholar]
  13. Hanson C. V., Riggs J. L., Lennette E. H. Photochemical inactivation of DNA and RNA viruses by psoralen derivatives. J Gen Virol. 1978 Aug;40(2):345–358. doi: 10.1099/0022-1317-40-2-345. [DOI] [PubMed] [Google Scholar]
  14. Hearst J. E., Thiry L. The photoinactivation of an RNA animal virus, vesicular stomatitis virus, with the aid of newly synthesized psoralen derivatives. Nucleic Acids Res. 1977;4(5):1339–1347. doi: 10.1093/nar/4.5.1339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hunter G. D., Millson G. C. Attempts to release the scrapie agent from tissue debris. J Comp Pathol. 1967 Jul;77(3):301–307. doi: 10.1016/0021-9975(67)90039-4. [DOI] [PubMed] [Google Scholar]
  16. Isaacs S. T., Shen C. K., Hearst J. E., Rapoport H. Synthesis and characterization of new psoralen derivatives with superior photoreactivity with DNA and RNA. Biochemistry. 1977 Mar 22;16(6):1058–1064. doi: 10.1021/bi00625a005. [DOI] [PubMed] [Google Scholar]
  17. Johnston B. H., Johnson M. A., Moore C. B., Hearst J. E. Psoralen-DNA photoreaction: controlled production of mono- and diadducts with nanosecond ultraviolet laser pulses. Science. 1977 Aug 26;197(4306):906–908. doi: 10.1126/science.887929. [DOI] [PubMed] [Google Scholar]
  18. Malone T. G., Marsh R. F., Hanson R. P., Semancik J. S. Evidence for the low molecular weight nature of scrapie agent. Nature. 1979 Apr 5;278(5704):575–576. doi: 10.1038/278575a0. [DOI] [PubMed] [Google Scholar]
  19. Marsh R. F., Malone T. G., Semancik J. S., Lancaster W. D., Hanson R. P. Evidence for an essential DNA component in the Scrapie agent. Nature. 1978 Sep 14;275(5676):146–147. doi: 10.1038/275146a0. [DOI] [PubMed] [Google Scholar]
  20. Marsh R. F., Semancik J. S., Medappa K. C., Hanson R. P., Rueckert R. R. Scrapie and transmissible mink encephalopathy: search for infectious nucleic acid. J Virol. 1974 May;13(5):993–996. doi: 10.1128/jvi.13.5.993-996.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. McClements W. L., Kaesberg P. Size and secondary structure of potato spindle tuber viroid. Virology. 1977 Feb;76(2):477–484. doi: 10.1016/0042-6822(77)90230-6. [DOI] [PubMed] [Google Scholar]
  22. McKinley M. P., Masiarz F. R., Prusiner S. B. Reversible chemical modification of the scrapie agent. Science. 1981 Dec 11;214(4526):1259–1261. doi: 10.1126/science.6795721. [DOI] [PubMed] [Google Scholar]
  23. Miles E. W. Modification of histidyl residues in proteins by diethylpyrocarbonate. Methods Enzymol. 1977;47:431–442. doi: 10.1016/0076-6879(77)47043-5. [DOI] [PubMed] [Google Scholar]
  24. Owens R. A., Diener T. O. RNA intermediates in potato spindle tuber viroid replication. Proc Natl Acad Sci U S A. 1982 Jan;79(1):113–117. doi: 10.1073/pnas.79.1.113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Owens R. A., Erbe E., Hadidi A., Steere R. L., Diener T. O. Separation and infectivity of circular and linear forms of potato spindle tuber viroid. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3859–3863. doi: 10.1073/pnas.74.9.3859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Prusiner S. B., Cochran S. P., Groth D. F., Downey D. E., Bowman K. A., Martinez H. M. Measurement of the scrapie agent using an incubation time interval assay. Ann Neurol. 1982 Apr;11(4):353–358. doi: 10.1002/ana.410110406. [DOI] [PubMed] [Google Scholar]
  27. Prusiner S. B., Groth D. F., Bildstein C., Masiarz F. R., McKinley M. P., Cochran S. P. Electrophoretic properties of the scrapie agent in agarose gels. Proc Natl Acad Sci U S A. 1980 May;77(5):2984–2988. doi: 10.1073/pnas.77.5.2984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Prusiner S. B., Groth D. F., Cochran S. P., Masiarz F. R., McKinley M. P., Martinez H. M. Molecular properties, partial purification, and assay by incubation period measurements of the hamster scrapie agent. Biochemistry. 1980 Oct 14;19(21):4883–4891. doi: 10.1021/bi00562a028. [DOI] [PubMed] [Google Scholar]
  29. Prusiner S. B., Groth D. F., McKinley M. P., Cochran S. P., Bowman K. A., Kasper K. C. Thiocyanate and hydroxyl ions inactivate the scrapie agent. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4606–4610. doi: 10.1073/pnas.78.7.4606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Prusiner S. B., McKinley M. P., Groth D. F., Bowman K. A., Mock N. I., Cochran S. P., Masiarz F. R. Scrapie agent contains a hydrophobic protein. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6675–6679. doi: 10.1073/pnas.78.11.6675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Prusiner S. B. Novel proteinaceous infectious particles cause scrapie. Science. 1982 Apr 9;216(4542):136–144. doi: 10.1126/science.6801762. [DOI] [PubMed] [Google Scholar]
  32. Raymer W. B., Diener T. O. Potato spindle tuber virus: a plant virus with properties of a free nucleic acid. I. Assay, extraction, and concentration. Virology. 1969 Mar;37(3):343–350. doi: 10.1016/0042-6822(69)90218-9. [DOI] [PubMed] [Google Scholar]
  33. Sanger H. L., Klotz G., Riesner D., Gross H. J., Kleinschmidt A. K. Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc Natl Acad Sci U S A. 1976 Nov;73(11):3852–3856. doi: 10.1073/pnas.73.11.3852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Semancik J. S., Weathers L. G. Exocortis virus: an infectious free-nucleic acid plant virus with unusual properties. Virology. 1972 Feb;47(2):456–466. doi: 10.1016/0042-6822(72)90281-4. [DOI] [PubMed] [Google Scholar]
  35. Sogo J. M., Koller T., Diener T. O. Potato spindle tuber viroid. X. Visualization and size determination by electron microscopy. Virology. 1973 Sep;55(1):70–80. doi: 10.1016/s0042-6822(73)81009-8. [DOI] [PubMed] [Google Scholar]
  36. Symons R. H. Avocado sunblotch viroid: primary sequence and proposed secondary structure. Nucleic Acids Res. 1981 Dec 11;9(23):6527–6537. doi: 10.1093/nar/9.23.6527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Visvader J. E., Gould A. R., Bruening G. E., Symons R. H. Citrus exocortis viroid: nucleotide sequence and secondary structure of an Australian isolate. FEBS Lett. 1982 Jan 25;137(2):288–292. doi: 10.1016/0014-5793(82)80369-4. [DOI] [PubMed] [Google Scholar]
  38. Ward R. L., Porter D. D., Stevens J. G. Nature of the scrapie agent: evidence against a viroid. J Virol. 1974 Nov;14(5):1099–1103. doi: 10.1128/jvi.14.5.1099-1103.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES