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Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gpl60

Nature volume 360, pages 358–361 (1992)Cite this article

Abstract

THE envelope glycoprotein of human immunodeficiency virus (HIV) initiates infection1 by mediating fusion of the viral envelope with the cell membrane. Fusion activity requires proteolytic cleavage of the gp160 protein into gp120 and gp41 at a site containing several arginine and lysine residues2. Activation at basic cleavage sites is observed with many membrane proteins of cellular and viral origin. We have recently found that the enzyme activating the haemagglutinin of fowl plague virus (FPV), an avian influenza virus, is furin3. Furin, a subtilisin-like eukaryotic endoprotease4–6, has a substrate specificity for the consensus amino-acid sequence Arg-X-Lys/Arg-Arg at the cleavage site7. We show here that the glycoprotein of HIV-1, which has the same protease recognition motif as the FPV haemagglutinin, is also activated by furin. Furthermore, we present evidence that peptidyl-chloromethyl ketones that have the Arg-X-Lys/Arg-Arg motif and which are specific inhibitors of furin3 interfere with cleavage of the HIV glycoprotein and hence its activation and the formation of infectious virus particles.

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Authors and Affiliations

  1. Institut für Virologie, Philips-Universität Marburg, Robert-Kochstrasse 17, 3550, Marburg, Germany

    Sabine Hallenberger, Hans-Dieter Klenk & Wolfgang Garten

  2. Institut für Angewandte Tumorvirologie am Deutschen Krebsforschungszentrum Heidelberg, Im Neuenheimer Feld 242, 6900, Heidelberg, 1, Germany

    Valerie Bosch

  3. Friedrich Miescher-lnstitut Basel, PO Box 2543, CH-4002, Basel, Switzerland

    Herbert Angliker & Elliott Shaw

Authors
  1. Sabine Hallenberger
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  2. Valerie Bosch
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  3. Herbert Angliker
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  4. Elliott Shaw
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  5. Hans-Dieter Klenk
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  6. Wolfgang Garten
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Hallenberger, S., Bosch, V., Angliker, H. et al. Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gpl60. Nature 360, 358–361 (1992). https://doi.org/10.1038/360358a0

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