Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160.

Abstract

The envelope glycoprotein of human immunodeficiency virus (HIV) initiates infection 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 residues. 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 furin. Furin, a subtilisin-like eukaryotic endoprotease, has a substrate specificity for the consensus amino-acid sequence Arg-X-Lys/Arg-Arg at the cleavage site. 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.

• Authors: S Hallenberger, V Bosch, H Angliker, E Shaw, H D Klenk, W Garten
• Journal: Nature (Nature) Vol. 360 Issue 6402 Pg. 358-61 (Nov 26 1992) ISSN: 0028-0836 [Print] England
• PMID: 1360148 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acid Chloromethyl Ketones
• Gene Products, env
• HIV Envelope Protein gp160
• Protein Precursors
• Subtilisins
• Furin

Topics

• Amino Acid Chloromethyl Ketones (pharmacology)
• Amino Acid Sequence
• CD4-Positive T-Lymphocytes (metabolism, microbiology)
• Consensus Sequence
• Furin
• Gene Expression
• Gene Products, env (genetics, metabolism)
• HIV Envelope Protein gp160
• HIV-1 (chemistry, physiology)
• HeLa Cells (metabolism)
• Humans
• Molecular Sequence Data
• Protein Precursors (genetics, metabolism)
• Substrate Specificity
• Subtilisins (antagonists & inhibitors, genetics, metabolism)
• Virus Replication (drug effects)