Correlation of proteolytic cleavage of F protein precursors in paramyxoviruses with expression of the , PACE4 and PC6 genes in mammalian cells Free

Abstract

The fusion (F) protein precursor of virulent Newcastle disease virus (NDV) strains and human parainfluenza virus type 3 (HPIV3) has a multibasic amino acid sequence at the cleavage site, and intracellular cleavage activation occurs in a variety of cells. The host protease responsible for the cleavage has been proposed to be a subtilisin-like protease (subtilase) such as furin (the product of the gene). We found that the lymphocyte cell lines MOLT-4, Ramos and Daudi, in addition to NALM6, lacked the ability to fully cleave the F protein precursor of virulent NDV. In contrast, MT4 as well as the non-lymphocyte cell lines HeLa and Hep2 cleaved the F protein precursor efficiently. To investigate the role of subtilases in proteolytic processing, we examined the gene expression of candidate subtilases, furin, PACE4 and PC6 in these cleavage-competent and -incompetent cells. Considerable expression of the gene was observed in the cleavage-competent cells, but little or no expression was detected in the cleavage- incompetent cells. PACE4 and PC6 gene expression was observed in some of the cleavage-competent cells but not in the cleavage-incompetent cells. These results suggest that furin is the protease responsible for cleavage activation of the F protein of virulent NDV strains in cultured mammalian cells and the possibility is raised that PACE4 and PC6 also participate in processing in some of the cells. On the other hand, the HPIV3 F protein was cleaved efficiently in lymphocyte cells deficient in subtilases, suggesting that an unknown protease other than furin, PACE4 or PC6 may be involved in the processing.

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1994-10-01
2024-03-28
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References

  1. Abenes G., Kida H., Yanagawa R. 1986; Antigenic mapping and functional analysis of the F protein of Newcastle disease virus using monoclonal antibodies. Archives of Virology 90:97–110
    [Google Scholar]
  2. Barr P. J. 1991; Mammalian subtilisins: the long-sought dibasic processing endoproteases. Cell 66:1–3
    [Google Scholar]
  3. Bresnahan P. A., Leduc R., Thomas L., Thorner J., Gibson H. L., Brake A. J., Barr P. J., Thomas G. 1990; Human fur gene encodes a yeast KEX2-like endoprotease that cleaves pro-beta-NGF in vivo. Journal of Cell Biology 111:2851–2859
    [Google Scholar]
  4. Fuller R. S., Brake A., Thorner J. 1989; Yeast prohormone processing enzyme (KEX2 gene product) is a Ca2+-dependent serine protease. Proceedings of the National Academy of Sciences, U.S.A 86:1434–1438
    [Google Scholar]
  5. Glickman R. L., Syddall R. J., Iorio R. M., Sheehan J. P., Bratt M. A. 1988; Quantitative basic residue requirements in the cleavage-activation site of the fusion glycoprotein as a determinant of virulence for Newcastle disease virus. Journal of Virology 62:354–356
    [Google Scholar]
  6. Gotoh B., Ohnishi Y., Inocencio N. M., Esaki E., Nakayama K., Barr P. J., Thomas G., Nagai Y. 1992; Mammalian subtilisin- related proteinases in cleavage activation of the paramyxovirus fusion glycoprotein: superiority of furin/PACE to PC2 or PC1/PC3. Journal of Virology 66:6391–6397
    [Google Scholar]
  7. Hallenberger S., Bosch V., Angliker H., Shaw E., Klenk H.-D., Garten W. 1992; Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gpl60. Nature; London: 360358–361
    [Google Scholar]
  8. Hatsuzawa K., Hosaka M., Nakagawa T., Nagase M., Shoda A., Murakami K., Nakayama K. 1990; Structure and expression of mouse furin, a yeast Kex2-related protease. Lack of processing of coexpressedprorenin in GH4C1 cells. Journal of Biological Chemistry 265:22075–22078
    [Google Scholar]
  9. Hatsuzawa K., Nakagawa M., Takahashi S., Takada K., Murakami K., Nakayama K. 1992; Purification and characterization of furin, a Kex2-like processing endoprotease, produced in Chinese hamster ovary cells. Journal of Biological Chemistry 267:16094–16099
    [Google Scholar]
  10. Kawahara N., Yang X. Z., Sakaguchi T., Kiyotani K., Nagai Y., Yoshida T. 1992; Distribution and substrate specificity of intracellular proteolytic processing enzyme(s) for paramyxovirus fusion glycoproteins. Journal of General Virology 73:583–590
    [Google Scholar]
  11. Kido H., Kamoshita K., Fukutomi A., Katunuma N. 1993; Processing protease for gpl60 human immunodeficiency virus type 1 envelope glycoprotein precursor in human T4+ lymphocytes. Purification and characterization. Journal of Biological Chemistry 268:13406–13413
    [Google Scholar]
  12. Kiefer M. C., Tucker J. E., Joh R., Landsberg K. E., Saltman D., Barr P. J. 1991; Identification of a second human subtilisin-like protease gene in the fes/fps region of chromosome 15. DNA and Cell Biology 10:757–769
    [Google Scholar]
  13. Klenk H.-D., Rott R. 1988; The molecular biology of influenza virus pathogenicity. Advances in Virus Research 34:247–281
    [Google Scholar]
  14. Mccune J. M., Rabin L. B., Feinberg M. B., Leiberman M., Kosek J. C., Reyes G. R., Weissman I. L. 1988; Endoproteolytic cleavage of gpl60 is required for the activation of human immunodeficiency virus. Cell 53:55–67
    [Google Scholar]
  15. Misumi Y., Oda K., Fujiwara T., Takami N., Tashiro K., Ikehara Y. 1991; Functional expression of furin demonstrating its intracellular localization and endoprotease activity for processing of proalbumin and complement pro-C3. Journal of Biological Chemistry 266:16954–16959
    [Google Scholar]
  16. Mizuno K., Nakamura T., Ohshima T., Tanaka S., Matsuo H. 1989; Characterization of Kex2-encoded endoprotease from yeast Saccharomyces cerevisiae. Biochemical and Biophysical Research Communications 159:305–311
    [Google Scholar]
  17. Molloy S. S., Bresnahan P. A., Leppla S. H., Klimpel K. R., Thomas G. 1992; Human furin is a calcium-dependent serine endoprotease that recognizes the sequence Arg-X-X-Arg and efficiently cleaves anthrax toxin protective antigen. Journal of Biological Chemistry 267:16396–16402
    [Google Scholar]
  18. Morikawa Y., Barsov E., Jones I. 1993; Legitimate and illegitimate cleavage of human immunodeficiency virus glycoproteins by furin. Journal of Virology 67:3601–3604
    [Google Scholar]
  19. Morrison T. G., Ward L., Semerjian A. 1985; Intracellular processing of the Newcastle disease virus fusion glycoprotein. Journal of Virology 53:851–857
    [Google Scholar]
  20. Nagai Y. 1993; Protease-dependent virus tropism and pathogenicity. Trends in Microbiology 1:81–87
    [Google Scholar]
  21. Nakagawa T., Hosaka M., Torii S., Watanabe T., Murakami K., Nakayama K. 1993; Identification and functional expression of a new member of the mammalian Kex2-like processing endoprotease family: its striking structural similarity to PACE4. Journal of Biochemistry, Tokyo 113:132–135
    [Google Scholar]
  22. Nakayama K., Hosaka M., Hatsuzawa K., Murakami K. 1991; Cloning and functional expression of a novel endoprotease involved in prohormone processing at dibasic sites. Journal of Biochemistry, Tokyo 109:803–806
    [Google Scholar]
  23. Roebroek A. J. M., Schalken J. A., Leunissen J. A. M., Onnekink C., Bloemers H. P. J., van de Ven W. J. M. 1986; Evolutionary conserved close linkage of the c-fes/fps proto-oncogene and genetic sequences encoding a receptor-like protein. EMBO Journal 5:2197–2202
    [Google Scholar]
  24. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Ehrlich H. A. 1988; Primer directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–491
    [Google Scholar]
  25. Sakaguchi T., Matsuda Y, Kawahara N., Kiyotani K., Katunuma N., Nagai Y., Yoshida T. 1991; Identification of endoprotease activity in the trans Golgi membranes of rat liver cells that specifically processes in vitro the fusion glycoprotein precursor of virulent Newcastle disease virus. Virology 184:504–512
    [Google Scholar]
  26. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: A Laboratory Manual, 2nd edn. New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  27. Spriggs M., Olmsted R., Venkatesan S., Coligan J., Collins P. 1986; Fusion glycoprotein of human parainfluenza virus type 3: nucleotide sequence of the gene, direct identification of the cleavage-activation site, and comparison with other paramyxoviruses. Virology 152:241–251
    [Google Scholar]
  28. Steiner D. F., Smeekens S. P., Ohagi S., Chan S. J. 1992; The new enzymology of precursor processing endoproteases. Journal of Biological Chemistry 267:23435–23438
    [Google Scholar]
  29. Stieneke-Gröber A., Vey M., Angliker H., Shaw E., Thomas G., Roberts C., Klenk H.-D., Garten W. 1992; Influenza virus haemagglutinin with multibasic cleavage site is activated by furin, a subtilisin-like endoprotease. EMBO Journal 11:2407–2414
    [Google Scholar]
  30. Toyoda T., Sakaguchi T., Imai K., Inocencio N. M., Gotoh B., Hamaguchi M., Nagai Y. 1987; Structural comparison of the cleavage-activation site of the fusion glycoprotein between virulent and avirulent strains of Newcastle disease virus. Virology 158:242–247
    [Google Scholar]
  31. van den Ouweland A. M., van Duijnhoven H. J., Keizer G. D., Dorssers L. C., van de Ven W. J. 1990; Structural homology between the human fur gene product and the subtilisin-like protease encoded by yeast KEX2. Nucleic Acids Research 18:664
    [Google Scholar]
  32. van Wyke Coelingh K. L., Winter C., Murphy B. R. 1985; Antigenic variation in the hemagglutinin-neuraminidase protein of human parainfluenza type 3 virus. Virology 143:569–582
    [Google Scholar]
  33. Wise R. J., Barr P. J., Wong P. A., Kiefer M. C., Brake A. J. 1990; Expression of a human proprotein processing enzyme: correct cleavage of the von Willebrand factor precursor at a paired basic amino acid site. Proceedings of the National Academy of Sciences, U.S.A 87:9378–9382
    [Google Scholar]
  34. Yoshida T., Nakayama Y., Nagura H., Toyoda T., Nishikawa K., Hamaguchi M., Nagai Y. 1986; Inhibition of the assembly of Newcastle disease virus by monensin. Virus Research 4:179–195
    [Google Scholar]
  35. Yoshida T., Takao S., Kiyotani K., Sakaguchi T. 1989; Endoproteolytic activation of Newcastle disease virus fusion proteins requires an intracellular acidic environment. Virology 170:571–574
    [Google Scholar]
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