Identification of R-peptides in envelope proteins of C-type retroviruses Free

Abstract

Activation of the murine leukaemia virus (MLV) envelope protein (Env) requires proteolytic cleavage of the R-peptide, a 16 amino acid C-terminal part of the cytoplasmic tail (C-tail) of Env. This paper demonstrates the presence of R-peptides in Env proteins of C-type retroviruses of simian, avian and porcine origin. Sequence alignment with the MLV C-tail led to the identification of a conserved hydrophobic protease cleavage motif located in the centre of retroviral Env protein C-tails. Expression of Env proteins, truncated at the predicted cleavage sites, of spleen necrosis virus (SNV), gibbon ape leukaemia virus and porcine endogenous retroviruses resulted in cell–cell fusion as monitored by microscopy and reporter gene fusion assays. Western blot analysis of MLV particles pseudotyped with the SNV Env protein demonstrated proteolytic cleavage of the SNV R-peptide by the MLV protease. Our data suggest that activation of membrane fusion by R-peptide cleavage is a common mode in C-type retroviruses.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-83-9-2241
2002-09-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/83/9/0832241a.html?itemId=/content/journal/jgv/10.1099/0022-1317-83-9-2241&mimeType=html&fmt=ahah

References

  1. Bateman A., Bullough F., Murphy S., Emiliusen L., Lavillette D., Cosset F. L., Cattaneo R., Russell S. J., Vile R. G. 2000; Fusogenic membrane glycoproteins as a novel class of genes for the local and immune-mediated control of tumor growth. Cancer Research 60:1492–1497
    [Google Scholar]
  2. Brody B. A., Rhee S. S., Sommerfelt M. A., Hunter E. 1992; A viral protease-mediated cleavage of the transmembrane glycoprotein of Mason–Pfizer monkey virus can be suppressed by mutations within the matrix protein. Proceedings of the National Academy of Sciences, USA 89:3443–3447
    [Google Scholar]
  3. Buchholz C. J., Stitz J., Cichutek K. 1999; Retroviral cell targeting vectors. Current Opinion in Molecular Therapeutics 1:613–621
    [Google Scholar]
  4. Christodoulopoulos I., Cannon P. M. 2001; Sequences in the cytoplasmic tail of the gibbon ape leukemia virus envelope protein that prevent its incorporation into lentivirus vectors. Journal of Virology 75:4129–4138
    [Google Scholar]
  5. Czauderna F., Fischer N., Boller K., Kurth R., Tonjes R. R. 2000; Establishment and characterization of molecular clones of porcine endogenous retroviruses replicating on human cells. Journal of Virology 74:4028–4038
    [Google Scholar]
  6. Eglitis M. A., Schneiderman R. D., Rice P. M., Eiden M. V. 1995; Evaluation of retroviral vectors based on the gibbon ape leukemia virus. Gene Therapy 2:486–492
    [Google Scholar]
  7. Engelstädter M., Bobkova M., Baier M., Stitz J., Holtkamp N., Chu T. H., Kurth R., Dornburg R., Buchholz C. J., Cichutek K. 2000; Targeting human T cells by retroviral vectors displaying antibody domains selected from a phage display library. Human Gene Therapy 11:293–303
    [Google Scholar]
  8. Fiane A. E., Mollnes T. E., Degre M. 2000; Pig endogenous retrovirus – a threat to clinical xenotransplantation?. APMIS 108:241–250
    [Google Scholar]
  9. Fielding A. K., Chapel-Fernandes S., Chadwick M. P., Bullough F. J., Cosset F. L., Russell S. J. 2000; A hyperfusogenic gibbon ape leukemia envelope glycoprotein: targeting of a cytotoxic gene by ligand display. Human Gene Therapy 11:817–826
    [Google Scholar]
  10. Gelinas C., Temin H. M. 1986; Nondefective spleen necrosis virus-derived vectors define the upper size limit for packaging reticuloendotheliosis viruses. Proceedings of the National Academy of Sciences, USA 83:9211–9215
    [Google Scholar]
  11. Green N., Shinnick T. M., Witte O., Ponticelli A., Sutcliffe J. G., Lerner R. A. 1981; Sequence-specific antibodies show that maturation of Moloney leukemia virus envelope polyprotein involves removal of a COOH-terminal peptide. Proceedings of the National Academy of Sciences, USA 78:6023–6027
    [Google Scholar]
  12. Henderson L. E., Sowder R., Copeland T. D., Smythers G., Oroszlan S. 1984; Quantitative separation of murine leukemia virus proteins by reversed-phase high-pressure liquid chromatography reveals newly described Gag and Env cleavage products. Journal of Virology 52:492–500
    [Google Scholar]
  13. Jiang A., Dornburg R. 1999; In vivo cell type-specific gene delivery with retroviral vectors that display single chain antibodies. Gene Therapy 6:1982–1987
    [Google Scholar]
  14. Jiang A., Chu T. H., Nocken F., Cichutek K., Dornburg R. 1998; Cell-type-specific gene transfer into human cells with retroviral vectors that display single-chain antibodies. Journal of Virology 72:10148–10156
    [Google Scholar]
  15. Kiernan R. E., Fried E. O. 1998; Cleavage of the murine leukemia virus transmembrane env protein by human immunodeficiency virus type 1 protease: transdominant inhibition by matrix mutations. Journal of Virology 72:9621–9627
    [Google Scholar]
  16. Martinez I., Dornburg R. 1995; Mapping of receptor binding domains in the envelope protein of spleen necrosis virus. Journal of Virology 69:4339–4346
    [Google Scholar]
  17. Nussbaum O., Broder C. C., Berger E. A. 1994; Fusogenic mechanisms of enveloped-virus glycoproteins analyzed by a novel recombinant vaccinia virus-based assay quantitating cell fusion-dependent reporter gene activation. Journal of Virology 68:5411–5422
    [Google Scholar]
  18. Ohno H., Aguilar R. C., Fournier M. C., Hennecke S., Cosson P., Bonifacino J. S. 1997; Interaction of endocytic signals from the HIV-1 envelope glycoprotein complex with members of the adaptor medium chain family. Virology 238:305–315
    [Google Scholar]
  19. Olsen K. E., Andersen K. B. 1999; Palmitoylation of the intracytoplasmic R peptide of the transmembrane envelope protein in Moloney murine leukemia virus. Journal of Virology 73:8975–8981
    [Google Scholar]
  20. Patience C., Switzer W. M., Takeuchi Y., Griffiths D. J., Goward M. E., Heneine W., Stoye J. P., Weiss R. A. 2001; Multiple groups of novel retroviral genomes in pigs and related species. Journal of Virology 75:2771–2775
    [Google Scholar]
  21. Ragheb J. A., Anderson W. F. 1994; pH-independent murine leukemia virus ecotropic envelope-mediated cell fusion: implications for the role of the R peptide and p12E TM in viral entry. Journal of Virology 68:3220–3231
    [Google Scholar]
  22. Rein A., Mirro J., Haynes J. G., Ernst S. M., Nagashima K. 1994; Function of the cytoplasmic domain of a retroviral transmembrane protein: p15E-p2E cleavage activates the membrane fusion capability of the murine leukemia virus Env protein. Journal of Virology 68:1773–1781
    [Google Scholar]
  23. Rice N. R., Henderson L. E., Sowder R. C., Copeland T. D., Oroszlan S., Edwards J. F. 1990; Synthesis and processing of the transmembrane envelope protein of equine infectious anemia virus. Journal of Virology 64:3770–3778
    [Google Scholar]
  24. Skehel J. J., Wiley D. C. 2000; Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annual Review of Biochemistry 69:531–569
    [Google Scholar]
  25. Soneoka Y., Cannon P. M., Ramsdale E. E., Griffiths J. C., Romano G., Kingsman S. M., Kingsman A. J. 1995; A transient three-plasmid expression system for the production of high titer retroviral vectors. Nucleic Acids Research 23:628–633
    [Google Scholar]
  26. Stitz J., Buchholz C. J., Engelstädter M., Uckert W., Bloemer U., Schmitt I., Cichutek K. 2000; Lentiviral vectors pseudotyped with envelope glycoproteins derived from gibbon ape leukemia virus and murine leukemia virus 10A1. Virology 273:16–20
    [Google Scholar]
  27. Takeuchi Y., Patience C., Magre S., Weiss R. A., Banerjee P. T., Le Tissier P., Stoye J. P. 1998; Host range and interference studies of three classes of pig endogenous retrovirus. Journal of Virology 72:9986–9991
    [Google Scholar]
  28. Ting Y. T., Wilson C. A., Farrell K. B., Chaudry G. J., Eiden M. V. 1998; Simian sarcoma-associated virus fails to infect Chinese hamster cells despite the presence of functional gibbon ape leukemia virus receptors. Journal of Virology 72:9453–9458
    [Google Scholar]
  29. Yang C., Compans R. W. 1997; Analysis of the murine leukemia virus R peptide: delineation of the molecular determinants which are important for its fusion inhibition activity. Journal of Virology 71:8490–8496
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-83-9-2241
Loading
/content/journal/jgv/10.1099/0022-1317-83-9-2241
Loading

Data & Media loading...

Most cited Most Cited RSS feed