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Genomic structures of viral agents in relation to the biosynthesis of selenoproteins

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Abstract

The genomes of both bacteria and eukaryotic organisms are known to encode selenoproteins, using the UGA codon for selenocysteine (SeC), and a complex cotranslational mechanism for SeC incorporation into polypeptide chains, involving RNA stem-loop structures. These common features and similar codon usage strongly suggest that this is an ancient evolutionary development. However, the possibility that some viruses might also encode selenoproteins remained unexplored until recently. Based on an analysis of the genomic structure of the human immunodeficiency virus HIV-1, we demonstrated that several regions overlapping known HIV genes have the potential to encode selenoproteins (Taylor et al.[31], J. Med. Chem. 37, 2637–2654 [1994]). This is provocative in the light of over-whelming evidence of a role for oxidative stress in AIDS pathogenesis, and the fact that a number of viral diseases have been linked to selenium (Se) deficiency, either in humans or by in vitro and animal studies. These include HIV-AIDS, hepatitis B linked to liver disease and cancer, Coxsackie virus B3, Keshan disease, and the mouse mammary tumor virus (MMTV), against which Se is a potent chemoprotective agent. There are also established biochemical mechanisms whereby extreme Se deficiency can induce a proclotting or hemorrhagic effect, suggesting that hemorrhagic fever viruses should also be examined for potential virally encoded selenoproteins. In addition to the RNA stem-loop structures required for SeC insertion at UGA codons, genomic structural features that may be required for selenoprotein synthesis can also include ribosomal frameshift sites and RNA pseudoknots if the potential selenoprotein module overlaps with another gene, which may prove to be the rule rather than the exception in viruses. One such pseudoknot that we predicted in HIV-1 has now been verified experimentally; a similar structure can be demonstrated in precisely the same location in the reverse transcriptase coding region of hepatitis B virus. Significant new findings reported here include the existence of highly distinctive glutathione peroxidase (GSH-Px)-related sequences in Coxsackie B viruses, new theoretical data related to a previously proposed potential selenoprotein gene overlapping the HIV protease coding region, and further evidence in support of a novel frameshift site in the HIVnef gene associated with a well-conserved UGA codon in the-1 reading frame.

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References

  1. S. Y. Yu, W. G. Li, Y. J. Zhu, W. P. Yu, and C. Hou,Biol. Trace Element Res. 20, 15–22 (1989).

    CAS  Google Scholar 

  2. S. Y. Yu, Y. J. Zhu, W. G. Li, Q. S. Huang, C. Z. Huang, Q. N. Zhang and C. Hou,Biol. Trace Element Res. 29, 289–294 (1991).

    Article  CAS  Google Scholar 

  3. J. Bai, S. Wu, K. Ge, X. Deng and C. Su,Acta Acad. Med. Sin. 2, 29–31 (1980).

    CAS  Google Scholar 

  4. M. A. Beck, P. C. Kolbeck, L. H. Rohr, Q. Shi, V. C. Morris and O. A. Levander,J. Med. Virol. 43, 166–170 (1994).

    Article  PubMed  CAS  Google Scholar 

  5. J. C. Hou, Z. Y. Jiang and Z. F. He,Chung Hua I Hsueh Tsa Chih 73, 645–646 (1993).

    PubMed  CAS  Google Scholar 

  6. G. N. Schrauzer, T. Molenaar, K. Kuehn and D. Waller,Biol. Trace Element Res. 20, 169–178 (1989).

    CAS  Google Scholar 

  7. B. M. Dworkin, G. P. Wormser, W. S. Rosenthal, S. K. Heier, M. Braunstein, L. Weiss, R. Jankowski, D. Levy and S. Weiselberg,Am. J. Gastroenterol. 80, 774 (1985).

    PubMed  CAS  Google Scholar 

  8. B. M. Dworkin, W. S. Rosenthal, G. P. Wormser and L. Weiss,J. Parenter. Enteral Nutr. 10, 405–407 (1986).

    CAS  Google Scholar 

  9. J. F. Zazzo, J. Chalas, A. Lafont, F. Camus and P. Chappuis,J. Parenter. Enteral Nutr. 12, 537–538 (1988).

    CAS  Google Scholar 

  10. B. M. Dworkin, W. S. Rosenthal, G. P. Wormser, L. Weiss, M. Nunez, C. Joline and A. Herp,Biol. Trace Element Res. 15, 167–177 (1988).

    Article  CAS  Google Scholar 

  11. B. M. Dworkin, P. P. Antonecchia, F. Smith, L. Weiss, M. Davidian, D. Rubin and W. S. Rosenthal,J. Parenter. Enteral Nutr. 13, 644–647 (1989).

    CAS  Google Scholar 

  12. L. Olmsted, G. N. Schrauzer, M. Flores-Arce and J. Dowd,Biol. Trace Element Res. 20, 59–65 (1989).

    CAS  Google Scholar 

  13. K. W. Beck, P. Schramel, A. Held, H. Jaeger and W. Kaboth,Biol. Trace Element Res. 25, 89–96 (1990).

    CAS  Google Scholar 

  14. A. L. Kavanaugh-McHugh, A. Ruff, E. Perlman, N. Hutton, J. Modlin and S. Rowe,J. Parenter. Enteral Nutr. 15, 347–351 (1991).

    CAS  Google Scholar 

  15. A. Cirelli, M. Ciardi, C. de-Simone, F. Sorice, R. Giordano, L. Ciaralli and S. Costantini,Clin. Biochem. 24, 211–214 (1991).

    Article  PubMed  CAS  Google Scholar 

  16. C. Allavena, B. Dousset, T. May, C. Amiel, F. Nabet-Belleville and P. Canton,Presse. Med. 20, 1737 (1991).

    PubMed  CAS  Google Scholar 

  17. E. Mantero-Atienza, R. S. Beach, M. C. Gavancho, R. Morgan, G. Shor-Posner and M. K. Fordyce-Baum,J. Parenter. Enteral Nutr. 15, 693–694 (1991).

    CAS  Google Scholar 

  18. J. P. Revillard, C. M. Vincent, A. E. Favier, M. J. Richard, M. Zittoun and M. D. Kazatchkine,J. Acquired Immune Defic. Syndr. 5, 637–638 (1992).

    CAS  Google Scholar 

  19. J. Constans, J. L. Pellegrin, E. Peuchant, M. F. Thomas, M. F. Dumon, C. Sergeant and M. Simonoff,Rev. Med. Interne. 14, 1003 (1993).

    PubMed  CAS  Google Scholar 

  20. A. Favier, C. Sappey, P. Leclerc, P. Faure and M. Micoud,Chem.-Biol. Interact. 91, 165–180 (1994).

    Article  PubMed  CAS  Google Scholar 

  21. B. M. Dworkin,Chem.-Biol. Interact. 91, 181–186 (1994).

    Article  PubMed  CAS  Google Scholar 

  22. R. Bologna, F. Indacochea, G. Shor-Posner, E. Mantero-Atienza, M. Grazziutti, M.-C. Sotomayor, M. Fletcher, C. Cabrejos, G. B. Scott and M. K. Baum.J. Nutr. Immunol. 3, 41–49 (1994).

    Article  Google Scholar 

  23. C. Sergeant, M. Simonoff, C. Hamon, E. Peuchant, M. F. Dumon, M. Clerc, M. J. Thomas, J. Constant, C. Conri, J. L. Pellegrin and B. Leng, inOxidative Stress, Cell Activation and Viral Infection C. Pasquier, ed., Birkhauser Verlag, Basel, pp. 341–351 (1994).

    Google Scholar 

  24. G. N. Schrauzer and J. Sacher,Chem.-Biol. Interact. 91, 199–206 (1994).

    Article  PubMed  CAS  Google Scholar 

  25. C. Allavena, B. Dousset, T. May, F. Dubois, P. Canton and F. Belleville,Biol. Trace Element Res. 47, 133–138 (1995).

    Article  CAS  Google Scholar 

  26. C. Sappey, S. Legrand-Poels, M. Best-Belpomme, A. Favier, B. Rentier and J. Piette,AIDS Res. Human Retroviruses 10, 1451–1461 (1994).

    CAS  Google Scholar 

  27. M. A. Beck, Q. Shi, V. C. Morris and O. A. Levander,Nature Med. 1, 433–436 (1995).

    Article  PubMed  CAS  Google Scholar 

  28. A. Bock, K. Forchhammer, J. Heider, W. Leinfelder, G. Sawers, B. Veprek and F. Zinoni,Mol. Microbiol. 5, 515–20 (1991).

    Article  PubMed  CAS  Google Scholar 

  29. M. J. Berry and P. R. Larsen,Biochem. Soc. Trans. 21, 827–832 (1993).

    PubMed  CAS  Google Scholar 

  30. B. K. Rima,Biochem. Soc. Trans. 1, 1–13 (1996).

    Google Scholar 

  31. E. W. Taylor, C. S. Ramanathan, R. K. Jalluri and R. G. Nadimpalli,J. Med. Chem. 37, 2637–2654 (1994).

    Article  PubMed  CAS  Google Scholar 

  32. E. W. Taylor, C. S. Ramanathan and R. G. Nadimpalli, in M. Witten, ed.,Computational Medicine, Public Health and Biotechnology: Building a Man in the Machine Part 1, World Scientific, London, pp. 285–309 (1996).

    Google Scholar 

  33. A. Sanchez, S. G. Trappier, B. W. J. Mahy, C. J. Peters and S. T. Nichol,Proc. Natl. Acad. Sci. USA 93, 3602–3607 (1996).

    Article  PubMed  CAS  Google Scholar 

  34. D. L. Hatfield, J. G. Levin, A. Rein and S. Oroszlan,Adv. Virus Res. 41, 193–239 (1992).

    PubMed  CAS  Google Scholar 

  35. T. Jacks, M. D. Power, F. R. Masiarz, P. A. Luciw, P. J. Barr and H. E. Varmus,Nature 331, 280–283 (1988).

    Article  PubMed  CAS  Google Scholar 

  36. T. G. Parslow, inHuman Retroviruses, B. R. Cullen, ed., Oxford University Press, New York, pp. 101–136, (1993).

    Google Scholar 

  37. T. Jacks, H. D. Madhani, F. R. Masiarz and H. E. Varmus,Cell 55, 447–458 (1988).

    Article  PubMed  CAS  Google Scholar 

  38. I. Brierley and J. A. Jenner,J. Mol. Biol. 227, 463–479 (1992).

    Article  PubMed  CAS  Google Scholar 

  39. R. B. Weiss,Current Opin. Cell Biol. 3, 1051–1055 (1991).

    Article  CAS  Google Scholar 

  40. M. Chammoro, N. Parkin and H. E. Varmus,Proc. Natl. Acad. Sci. USA 89, 713–717 (1992).

    Article  Google Scholar 

  41. E. ten Dam, K. Pleij and D. Draper,Biochemistry 31, 11,665–11,676 (1992).

    CAS  Google Scholar 

  42. J. Gallant and D. Lindsley,Biochem. Soc. Trans. 21, 817–821 (1993).

    PubMed  CAS  Google Scholar 

  43. M. H. de Smit, J. van Duin, P. H. van Knippenberg and G. H. van Eijk,Gene 143, 43–47 (1994).

    Article  PubMed  Google Scholar 

  44. Q. Shen, F. F. Chu and P. E. Newburger,J. Biol. Chem. 268, 11463–9 (1993).

    PubMed  CAS  Google Scholar 

  45. M. J. Berry, L. Banu, J. W. Harney and P. R. Larsen,EMBO J. 12, 3315–3322 (1993).

    PubMed  CAS  Google Scholar 

  46. J.-M. A. Battigello, M. Cui, S. Roshong and B. Carter,Bioorganic Med. Chem. 3, 839–849 (1995).

    Article  CAS  Google Scholar 

  47. E. W. Taylor, C. S. Ramanathan, R. G. Nadimpalli, and R. F. Schinazi,Antiviral Res. 26, A271, #86 (1995).

    Google Scholar 

  48. T. G. Senkevich, J. J. Bugert, J. R. Sisler, E. V. Koonin, G. Darai, and B. Moss,Science 273, 813–816 (1996).

    Article  PubMed  CAS  Google Scholar 

  49. R. G. Nadimpalli, J. A. Hamilton, A. Thakur, R. G. Dean, E. W. Taylor, and B. M. Blumberg,Virus Res., submitted for publication (1997).

  50. J. Engel,FEBS Lett. 251, 1–7 (1989).

    Article  PubMed  CAS  Google Scholar 

  51. A. Opgenorth, N. Nation, K. Graham and G. McFadden,Virology 192, 701–709 (1993).

    Article  PubMed  CAS  Google Scholar 

  52. T. M. Buttke and P. A. Sandstrom,Free Radical Res. 22, 389–397 (1994).

    Google Scholar 

  53. Z. Du, D. P. Giedroc and D. W. Hoffman,Biochemistry 35, 4187–4198 (1996).

    Article  PubMed  CAS  Google Scholar 

  54. Y. Wang, J. F. Holland, I. J. Bleiweiss, S. Melana, X. Liu, I. Pelisson, A. Cantarella, K. Stellrecht, S. Mani, and B. G.-T. Pogo,Cancer Res. 55, 5173–5179 (1995).

    PubMed  CAS  Google Scholar 

  55. C. S. Ramanathan and E. W. Taylor, Computational genomic analysis of hemorrhagic fever viruses.Biol. Trace Element Res. 56, 93–106 (1997).

    CAS  Google Scholar 

  56. F. Wong-Staal, R. C. Gallo, N. T. Chang, J. Ghrayeb, T. S. Papas, J. A. Lautenberger, M. L. Pearson, S. R. Petteway Jr., L. Ivanoff, K. Baumeister, E. A. Whitehorn, J. A. Rafalski, E. R. Doran, S. J. Joseph, B. Starcich, K. J. Livak, R. Patarca, W. A. Haseltine, and L. Ratner, Complete nucleotide sequence of the aids virus, htlv-iii,Nature 313, 277–284 (1985).

    Article  Google Scholar 

  57. G. N. Schrauzer, D. A. White and C. J. Schneider,Bioinorg. Chem. 6, 265–270 (1976).

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Computational Center for Molecular Structure and Design, The University of Georgia, 30601-2352, Athens, GA

    Ethan Will Taylor, Ram Gopal Nadimpalli & Chandra Sekar Ramanathan

  2. Department of Medicinal Chemistry, The University of Georgia, 30601-2352, Athens, GA

    Ethan Will Taylor, Ram Gopal Nadimpalli & Chandra Sekar Ramanathan

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  1. Ethan Will Taylor
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Taylor, E.W., Nadimpalli, R.G. & Ramanathan, C.S. Genomic structures of viral agents in relation to the biosynthesis of selenoproteins. Biol Trace Elem Res 56, 63–91 (1997). https://doi.org/10.1007/BF02778984

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