1887

Abstract

Recent studies have revealed that ‘human retrovirus-5’ sequences found in human samples belong to a rabbit endogenous retrovirus family named RERV-H. A part of the region of the RERV-H genome was amplified by PCR from DNA in human samples and several forms of RERV-H protease were expressed in bacteria. The RERV-H protease was able to cleave itself from a precursor protein and was also able to cleave the RERV-H Gag polyprotein precursor whereas a form of the protease with a mutation engineered into the active site was inactive. Potential N- and C-terminal autocleavage sites were characterized. The RERV-H protease was sensitive to pepstatin A, showing it to be an aspartic protease. Moreover, it was strongly inhibited by PYVPheStaAMT, a pseudopeptide inhibitor specific for Mason–Pfizer monkey virus and avian myeloblastosis-associated virus. A structural model of the RERV-H protease was constructed that, together with the activity data, confirms that this is a retroviral aspartic protease.

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2003-01-01
2024-03-29
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References

  1. Berman H. M., Westbrook J., Feng Z., Gilliland G., Bhat T. N., Weissig H., Shindyalov I. N., Bourne P. E. 2000; The Protein Data Bank. Nucleic Acids Res 28:235–242
    [Google Scholar]
  2. Bianchi M., Boigegrain R. A., Castro B., Coletti-Previero M. A. 1990; N-terminal domain of pepsin as a model for retroviral dimeric aspartyl protease. Biochem Biophys Res Commun 167:339–344
    [Google Scholar]
  3. Brand A., Griffiths D. J., Herve C., Mallon E., Venables P. J. 1999; Human retrovirus-5 in rheumatic disease. J Autoimmun 13:149–154
    [Google Scholar]
  4. Darke P. L., Leu C. T., Davis L. J., Heimbach J. C., Diehl R. E., Hill W. S., Dixon R. A., Sigal I. S. 1989; Human immunodeficiency virus protease. Bacterial expression and characterization of the purified aspartic protease. J Biol Chem 264:2307–2312
    [Google Scholar]
  5. Davies D. R. 1990; The structure and function of the aspartic proteinases. Annu Rev Biophys Biomol Struct 19:189–215
    [Google Scholar]
  6. Dean C. J., Gyure L. A., Hall J. G., Styles J. M. 1986; Production of IgA-secreting rat X rat hybridomas. Methods Enzymol 121:52–59
    [Google Scholar]
  7. Debouck C., Gorniak J. G., Strickler J. E., Meek T. D., Metcalf B. W., Rosenberg M. 1987; Human immunodeficiency virus protease expressed in Escherichia coli exhibits autoprocessing and specific maturation of the Gag precursor. Proc Natl Acad Sci U S A 84:8903–8906
    [Google Scholar]
  8. Dreyer G. B., Metcalf B. W., Tomaszek T. A. Jr & 9 other authors; 1989; Inhibition of human immunodeficiency virus 1 protease in vitro: rational design of substrate analogue inhibitors. Proc Natl Acad Sci U S A 869752–9756
    [Google Scholar]
  9. Elder J. H., Lerner D. L., Hasselkus-Light C. S., Fontenot D. J., Hunter E., Luciw P. A., Montelaro R. C., Phillips T. R. 1992; Distinct subsets of retroviruses encode dUTPase. J Virol 661791–1794
    [Google Scholar]
  10. Evan G. I., Lewis G. K., Ramsay G., Bishop J. M. 1985; Isolation of monoclonal antibodies specific for human c- myc proto-oncogene product. Mol Cell Biol 5:3610–3616
    [Google Scholar]
  11. Graves M. C., Lim J. J., Heimer E. P., Kramer R. A. 1988; An 11-kDa form of human immunodeficiency virus protease expressed in Escherichia coli is sufficient for enzymatic activity. Proc Natl Acad Sci U S A 852449–2453
    [Google Scholar]
  12. Griffiths D. J. 1996; Investigation of a novel retroviral element isolated from human salivary gland . PhD thesis University of London; London, UK:
  13. Griffiths D. J., Venables P. J., Weiss R. A., Boyd M. T. 1997; A novel exogenous retrovirus sequence identified in humans. J Virol 71:2866–2872
    [Google Scholar]
  14. Griffiths D. J., Cooke S. P., Herve C. 11 other authors 1999; Detection of human retrovirus 5 in patients with arthritis and systemic lupus erythematosus. Arthritis Rheum 42:448–454
    [Google Scholar]
  15. Griffiths D. J., Voisset C., Venables P. J. W., Weiss R. A. 2002; Novel endogenous retrovirus of rabbits previously identified as human retrovirus 5. J Virol 76:7094–7102
    [Google Scholar]
  16. Grinde B., Cameron C. E., Leis J., Weber I. T., Wlodawer A., Burstein H., Skalka A. M. 1992; Analysis of substrate interactions of the Rous sarcoma virus wild type and mutant proteases and human immunodeficiency virus-1 protease using a set of systematically altered peptide substrates. J Biol Chem 267:9491–9498
    [Google Scholar]
  17. Gustchina A., Kervinen J., Powell D. J., Zdanov A., Kay J., Wlodawer A. 1996; Structure of equine infectious anemia virus proteinase complexed with an inhibitor. Protein Sci 51453–1465
    [Google Scholar]
  18. Hansen J., Billich S., Schulze T., Sukrow S., Moelling K. 1988; Partial purification and substrate analysis of bacterially expressed HIV protease by means of monoclonal antibody. EMBO J 71785–1791
    [Google Scholar]
  19. Hatfield D. L., Levin J. G., Rein A., Oroszlan S. 1992; Translational suppression in retroviral gene expression. Adv Virus Res 41:193–239
    [Google Scholar]
  20. Hayakawa T., Misumi Y., Kobayashi M., Yamamoto Y., Fujisawa Y. 1992; Requirement of N- and C-terminal regions for enzymatic activity of human T-cell leukemia virus type I protease. Eur J Biochem 206:919–925
    [Google Scholar]
  21. Hill J., Phylip L. H. 1997; Bacterial aspartic proteinases. FEBS Lett 409357–360
    [Google Scholar]
  22. Hoog S. S., Towler E. M., Zhao B., Doyle M. L., Debouck C., Abdel-Meguid S. S. 1996; Human immunodeficiency virus protease ligand specificity conferred by residues outside of the active site cavity. Biochemistry 3510279–10286
    [Google Scholar]
  23. Hruskova-Heidingsfeldova O., Andreansky M., Fabry M., Blaha I., Strop P., Hunter E. 1995; Cloning, bacterial expression, and characterization of the Mason–Pfizer monkey virus proteinase. J Biol Chem 270:15053–15058
    [Google Scholar]
  24. Katoh I., Yoshinaka Y., Rein A., Shibuya M., Odaka T., Oroszlan S. 1985; Murine leukemia virus maturation: protease region required for conversion from ‘immature’ to ‘mature’ core form and for virus infectivity. Virology 145280–292
    [Google Scholar]
  25. Katoh I., Yasunaga T., Ikawa Y., Yoshinaka Y. 1987; Inhibition of retroviral protease activity by an aspartyl proteinase inhibitor. Nature 329654–656
    [Google Scholar]
  26. Kervinen J., Lubkowski J., Zdanov A. 7 other authors 1998; Toward a universal inhibitor of retroviral proteases: comparative analysis of the interactions of LP-130 complexed with proteases from HIV-1. FIV, and EIAV. Protein Sci 7:2314–2323
    [Google Scholar]
  27. Kohl N. E., Emini E. A., Schleif W. A., Davis L. J., Heimbach J. C., Dixon R. A., Scolnick E. M., Sigal I. S. 1988; Active human immunodeficiency virus protease is required for viral infectivity. Proc Natl Acad Sci U S A 854686–4690
    [Google Scholar]
  28. Kozireva S., Lejniece S., Blomberg J., Murovska M. 2001; Human retrovirus type 5 sequences in non-Hodgkin's lymphoma of T cell origin. AIDS Res Hum Retroviruses 17953–956
    [Google Scholar]
  29. Krohn A., Redshaw S., Ritchie J. C., Graves B. J., Hatada M. H. 1991; Novel binding mode of highly potent HIV-proteinase inhibitors incorporating the (R)-hydroxyethylamine isostere. J Med Chem 34:3340–3342
    [Google Scholar]
  30. Leuthardt A., Roesel J. L. 1993; Cloning, expression and purification of a recombinant poly-histidine-linked HIV-1 protease. FEBS Lett 326275–280
    [Google Scholar]
  31. Miller M., Jaskolski M., Rao J. K., Leis J., Wlodawer A. 1989; Crystal structure of a retroviral protease proves relationship to aspartic protease family. Nature 337576–579
    [Google Scholar]
  32. Mueller-Lantzsch N., Sauter M., Weiskircher A., Kramer K., Best B., Buck M., Grasser F. 1993; Human endogenous retroviral element K10 (HERV-K10) encodes a full-length gag homologous 73-kDa protein and a functional protease. AIDS Res Hum Retroviruses 9343–350
    [Google Scholar]
  33. Murovska M., Lejniece S., Kozireva S., Koulikovska M., Yin H., Blomberg J. 2000; Human retrovirus 5 sequences in peripheral blood cells of patients with B-cell non-Hodgkin's lymphoma. Int J Cancer 85:762–770
    [Google Scholar]
  34. Nam S. H., Hatanaka M. 1986; Identification of a protease gene of human T-cell leukemia virus type I (HTLV-I) and its structural comparison. Biochem Biophys Res Commun 139129–135
    [Google Scholar]
  35. Orengo C. A. 1999; CORA – topological fingerprints for protein structural families. Protein Sci 8:699–715
    [Google Scholar]
  36. Pichova I., Strop P., Sedlacek J. 7 other authors 1992; Isolation, biochemical characterization and crystallization of the p15gag proteinase of myeloblastosis associated virus expressed in E coli . Int J Biochem 24:235–242
    [Google Scholar]
  37. Rao J. K., Erickson J. W., Wlodawer A. 1991; Structural and evolutionary relationships between retroviral and eucaryotic aspartic proteinases. Biochemistry 304663–4671
    [Google Scholar]
  38. Ratner L., Haseltine W., Patarca R. 7 other authors 1985; Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature 313:277–284
    [Google Scholar]
  39. Rigby S. P., Griffiths D. J., Jarrett R. F., Weiss R. A., Venables P. J. 1998; A new human retrovirus: a role in lymphoma?. Am J Med 104:99–100
    [Google Scholar]
  40. Sali A., Blundell T. L. 1993; Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234:779–815
    [Google Scholar]
  41. Sambrook J. E., Fritsch F., Maniatis T. 1989 Molecular Cloning: a Laboratory Manual , 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  42. Sellos-Moura M., Vogt V. M. 1996; Proteolytic activity of purified avian sarcoma and leukemia virus NC-PR protein expressed in Escherichia coli . Virology 221335–345
    [Google Scholar]
  43. Sommerfelt M. A., Petteway S. R. Jr, Dreyer G. B., Hunter E. 1992; Effect of retroviral proteinase inhibitors on Mason–Pfizer monkey virus maturation and transmembrane glycoprotein cleavage. J Virol 664220–4227
    [Google Scholar]
  44. Stříšovský K., Smrz D., Fehrmann F., Krausslich H. G., Konvalinka J. 2002; The murine endogenous retrovirus MIA14 encodes an active aspartic proteinase that is functionally similar to proteinases from D-type retroviruses. Arch Biochem Biophys 398261–268
    [Google Scholar]
  45. Umezawa H., Aoyagi T., Morishima H., Matsuzaki M., Hamada M. 1970; Pepstatin, a new pepsin inhibitor produced by actinomycetes. J Antibiot (Tokyo) 23:259–262
    [Google Scholar]
  46. Vogt V. M., Wight A., Eisenman R. 1979; In vitro cleavage of avian retrovirus Gag proteins by viral protease p15. Virology 98154–167
    [Google Scholar]
  47. Wan M., Takagi M., Loh B. N., Xu X. Z., Imanaka T. 1996; Autoprocessing: an essential step for the activation of HIV-1 protease. Biochem J 316569–573
    [Google Scholar]
  48. Wlodawer A., Gustchina A. 2000; Structural and biochemical studies of retroviral proteases. Biochim Biophys Acta 1477. 16–34
  49. Wlodawer A., Miller M., Jaskolski M. 7 other authors 1989; Conserved folding in retroviral proteases: crystal structure of a synthetic HIV-1 protease. Science 245616–621
    [Google Scholar]
  50. Wu J., Adomat J. M., Ridky T. W., Louis J. M., Leis J., Harrison R. W., Weber I. T. 1998; Structural basis for specificity of retroviral proteases. Biochemistry 374518–4526
    [Google Scholar]
  51. Zhang Z. Y., Poorman R. A., Maggiora L. L., Heinrikson R. L., Kezdy F. J. 1991; Dissociative inhibition of dimeric enzymes. Kinetic characterization of the inhibition of HIV-1 protease by its COOH-terminal tetrapeptide. J Biol Chem 266:15591–15594
    [Google Scholar]
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