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. 1975 Aug 1;142(2):483–494. doi: 10.1084/jem.142.2.483

RNA-instructed DNA polymerase activity in a cytoplasmic particulate fraction in brains from Guamanian patients

PMCID: PMC2189894  PMID: 49390

Abstract

Nervous system tissues from a number of patients with idiopathic neurological disorders were examined for biochemical evidence of RNA tumor virus infection. RNase-sensitive DNA polymerase activity was found in a cytoplasmic particulate fraction from two patients with Guamanian amyotrophic lateral sclerosis (ALS) but not in brains from two normal U.S. individuals. The buoyant density of the enzyme- containing fraction was 1.16-1.18 g/ml and could be converted to a denser region of the gradient (1.24 g/ml) by treatment with the nonionic surfactant, Sterox. The cation and detergent requirements for the endogenous RNase-sensitive DNA polymerase reaction were determined. The early (5 min) endogenous reverse transcriptase product was analyzed by cesium sulfate gradient centrifugation. RNase- and heat-sensitive RNA-DNA hybrids were detected in the product analysis of two ALS, one Parkinsonism-dementia (PD) brain, and two brains from asymptomatic Chamorros but not in brains from normal U.S. individuals and a number of patients with neuro-psychiatric disorders. The DNA product was a 4.5S heteropolymer that hybridized more extensively to RNA extracted from the enzyme-containing pellet from PD brain as compared to a similar fraction from normal U.S. brain. The DNA product appeared to be unrelated to Rausvher or visna virus 70S RNA as determined by RNA-[- 3H]DNA hybridization.

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Selected References

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

  1. Bader J. P., Brown N. R., Bader A. V. Characteristics of cores of avian leuko-sarcoma viruses. Virology. 1970 Aug;41(4):718–728. doi: 10.1016/0042-6822(70)90436-8. [DOI] [PubMed] [Google Scholar]
  2. Britten R. J., Kohne D. E. Repeated sequences in DNA. Hundreds of thousands of copies of DNA sequences have been incorporated into the genomes of higher organisms. Science. 1968 Aug 9;161(3841):529–540. doi: 10.1126/science.161.3841.529. [DOI] [PubMed] [Google Scholar]
  3. Brody J. A., Hirano A., Scott R. M. Recent neuropathologic observations in amyotrophic lateral sclerosis and parkinsonism-dementia of Guam. Neurology. 1971 May;21(5):528–536. doi: 10.1212/wnl.21.5.528. [DOI] [PubMed] [Google Scholar]
  4. Chang L. M., Bollum F. J. Deoxynucleotide-polymerizing enzymes of calf thymus gland. V. Homogeneous terminal deoxynucleotidyl transferase. J Biol Chem. 1971 Feb 25;246(4):909–916. [PubMed] [Google Scholar]
  5. Chattopadhyay S. K., Rowe W. P., Teich N. M., Lowy D. R. Definitive evidence that the murine C-type virus inducing locus Akv-1 is viral genetic material. Proc Natl Acad Sci U S A. 1975 Mar;72(3):906–910. doi: 10.1073/pnas.72.3.906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chiu J. F., Sung S. C. Particulate form of DNA polymerase in rat brain. Nat New Biol. 1972 Oct 11;239(93):176–178. doi: 10.1038/newbio239176a0. [DOI] [PubMed] [Google Scholar]
  7. Eldridge R., Ryan E., Rosario J., Brody J. A. Amyotrophic lateral sclerosis and parkinsonism dementia in a migrant population from Guam. Neurology. 1969 Nov;19(11):1029–1037. doi: 10.1212/wnl.19.11.1029. [DOI] [PubMed] [Google Scholar]
  8. Feldman S. P., Schlom J., Spiegelman S. Further evidence for oncornaviruses in human milk: the production of cores. Proc Natl Acad Sci U S A. 1973 Jul;70(7):1976–1980. doi: 10.1073/pnas.70.7.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gallo R. C., Miller N. R., Saxinger W. C., Gillespie D. Primate RNA tumor virus-like DNA synthesized endogenously by RNA-dependent DNA polymerase in virus-like particles from fresh human acute leukemic blood cells. Proc Natl Acad Sci U S A. 1973 Nov;70(11):3219–3224. doi: 10.1073/pnas.70.11.3219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gardner M. B., Henderson B. E., Officer J. E., Rongey R. W., Parker J. C., Oliver C., Estes J. D., Huebner R. J. A spontaneous lower motor neuron disease apparently caused by indigenous type-C RNA virus in wild mice. J Natl Cancer Inst. 1973 Oct;51(4):1243–1254. doi: 10.1093/jnci/51.4.1243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gibbs C. J., Jr, Gajdusek D. C. Amyotrophic lateral sclerosis, Parkinson's disease, and the amyotrophic lateral sclerosis-Parkinsonism-dementia complex on Guam: a review and summary of attempts to demonstrate infection as the aetiology. J Clin Pathol Suppl (R Coll Pathol) 1972;6:132–140. [PMC free article] [PubMed] [Google Scholar]
  12. Gillespie D., Takemoto K., Robert M., Gallo R. C. Polyadenylic acid in Visna virus RNA. Science. 1973 Mar 30;179(4080):1328–1330. doi: 10.1126/science.179.4080.1328. [DOI] [PubMed] [Google Scholar]
  13. Gulati S. C., Axel R., Spiegelman S. Detection of RNA-instructed DNA polymerase and high molecular weight RNA in malignant tissue. Proc Natl Acad Sci U S A. 1972 Aug;69(8):2020–2024. doi: 10.1073/pnas.69.8.2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Haase A. T., Varmus H. E. Demonstration of a DNA provirus in the lytic growth of visna virus. Nat New Biol. 1973 Oct 24;245(147):237–239. doi: 10.1038/newbio245237a0. [DOI] [PubMed] [Google Scholar]
  15. KURLAND L. T. Epidemiologic investigations of amyotrophic lateral sclerosis. III. A genetic interpretation of incidence and geographic distribution. Proc Staff Meet Mayo Clin. 1957 Aug 21;32(17):449–462. [PubMed] [Google Scholar]
  16. Kurland L. T. An appraisal of the neurotoxicity of cycad and the etiology of amyotrophic lateral sclerosis on Guam. Fed Proc. 1972 Sep-Oct;31(5):1540–1542. [PubMed] [Google Scholar]
  17. Lee S. Y., Mendecki J., Brawerman G. A polynucleotide segment rich in adenylic acid in the rapidly-labeled polyribosomal RNA component of mouse sarcoma 180 ascites cells. Proc Natl Acad Sci U S A. 1971 Jun;68(6):1331–1335. doi: 10.1073/pnas.68.6.1331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lin F. H., Thormar H. Characterization of ribonucleic acid from visna virus. J Virol. 1971 May;7(5):582–587. doi: 10.1128/jvi.7.5.582-587.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Officer J. E., Tecson N., Estes J. D., Fontanilla E., Rongey R. W., Gardner M. B. Isolation of a neurotropic type C virus. Science. 1973 Sep 7;181(4103):945–947. doi: 10.1126/science.181.4103.945. [DOI] [PubMed] [Google Scholar]
  20. Reitz M. S., Jr, Smith R. G., Roseberry E. A., Gallo R. C. DNA-direced and RNA-primed DNA synthesis in microsomal and mitochondrial fractions of normal human lymphocytes. Biochem Biophys Res Commun. 1974 Apr 8;57(3):934–948. doi: 10.1016/0006-291x(74)90635-4. [DOI] [PubMed] [Google Scholar]
  21. Ruprecht R. M., Goodman N. C., Spiegelman S. Conditions for the selective synthesis of DNA complementary to template RNA. Biochim Biophys Acta. 1973 Jan 19;294(2):192–203. [PubMed] [Google Scholar]
  22. STUDIER F. W. SEDIMENTATION STUDIES OF THE SIZE AND SHAPE OF DNA. J Mol Biol. 1965 Feb;11:373–390. doi: 10.1016/s0022-2836(65)80064-x. [DOI] [PubMed] [Google Scholar]
  23. Schlom J., Harter D. H., Burny A., Spiegelman S. DNA polymerase activities in varions of visna virus, a causative agent of a "slow" neurological disease. Proc Natl Acad Sci U S A. 1971 Jan;68(1):182–186. doi: 10.1073/pnas.68.1.182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schlom J., Spiegelman S. Simultaneous detection of reverse transcriptase and high molecular weight RNA unique to oncogenic RNA viruses. Science. 1971 Nov 19;174(4011):840–843. doi: 10.1126/science.174.4011.840. [DOI] [PubMed] [Google Scholar]
  25. Spiegelman S., Burny A., Das M. R., Keydar J., Schlom J., Travnicek M., Watson K. DNA-directed DNA polymerase activity in oncogenic RNA viruses. Nature. 1970 Sep 5;227(5262):1029–1031. doi: 10.1038/2271029a0. [DOI] [PubMed] [Google Scholar]
  26. Stanhope J. M., Brody J. A., Morris C. E. Epidemiologic features of amyotropic lateral sclerosis and parkinsonism-dementia in Guam, Mariana Islands. Int J Epidemiol. 1972 Autumn;1(3):199–210. doi: 10.1093/ije/1.3.199. [DOI] [PubMed] [Google Scholar]
  27. Stansly P. G. Non-oncogenic infectious agents associated with experimental tumors. Prog Exp Tumor Res. 1965;7:224–258. doi: 10.1159/000391382. [DOI] [PubMed] [Google Scholar]
  28. Stone L. B., Scolnick E., Takemoto K. K., Aaronson S. A. Visna virus: a slow virus with an RNA dependent DNA polymerase. Nature. 1971 Jan 22;229(5282):257–258. doi: 10.1038/229257a0. [DOI] [PubMed] [Google Scholar]
  29. Stromberg K. Surface-active agents for isolation of the core component of avian myeloblastosis virus. J Virol. 1972 Apr;9(4):684–697. doi: 10.1128/jvi.9.4.684-697.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Szijan I., Burdman J. A. DNA polymerase activity in fractions from brain cell nuclei. Brain Res. 1974 Jun 28;73(3):563–567. doi: 10.1016/0006-8993(74)90681-7. [DOI] [PubMed] [Google Scholar]
  31. THORMAR H. An electron microscope study of tissue cultures infected with visna virus. Virology. 1961 Aug;14:463–475. doi: 10.1016/0042-6822(61)90339-7. [DOI] [PubMed] [Google Scholar]
  32. Viola M. V., White L. R. Differences in murine leukaemia virus-specific DNA sequences in normal and malignant cells. Nature. 1973 Dec 21;246(5434):485–487. doi: 10.1038/246485a0. [DOI] [PubMed] [Google Scholar]

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