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

  title={Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gpl60},
  author={Sabine Hallenberger and Valerie Bosch and Herbert Angliker and Elliott Shaw and Hans Dieter Klenk and Wolfgang Garten},
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… 
Polyarginine Inhibits gp160 Processing by Furin and Suppresses Productive Human Immunodeficiency Virus Type 1 Infection*
The data support that inhibitors of proteolytic processing of gp160 may be useful for combating human immunodeficiency virus-1 and that polyarginine represents a lead example of such inhibitors.
The role of eukaryotic subtilisin-like endoproteases for the activation of human immunodeficiency virus glycoproteins in natural host cells
Among the known members of the subtilisin family, only furin and LPC/PC7 fulfill the requirements of a protease responsible for in vivo activation of HIV envelope glycoproteins.
Engineered serine protease inhibitor prevents furin-catalyzed activation of the fusion glycoprotein and production of infectious measles virus
Results show that a mature F protein is not required for the assembly of MV but is crucial for virus infectivity, and the engineered serpin may offer a novel molecular antiviral approach against MV.
Structural investigation of the HIV-1 envelope glycoprotein gp160 cleavage site.
The solution structural analysis of a 19-residue synthetic peptide, p498, which spans the two gp160-processing sites 1 and 2, and is properly digested by furin at site 1, is reported on.
Natural variation in the amino acid sequence around the HIV type 1 glycoprotein 160 cleavage site and its effect on cleavability, subunit association, and membrane fusion.
Four constructs derived from two isolates of the same patient showed an unusual gp41 N terminus and a slightly diminished fusion capacity due to a decreased cleavability, which indicates that the major determinants for the SI and NSI phenotypes are not located around the gp160 cleavage site and that the N termini plays a minor role in the processing and fusion capacity of wild-type HIV-1 isolates.
Kex2p: a model for cellular endoprotease processing human immunodeficiency virus type 1 envelope glycoprotein precursor.
Results show that Kex2p cleaves both the HIV-1 envelope glycoprotein precursor and a synthetic peptide mimicking the cleavage site of AIDS-1 gp160 at the dibasic site, suggesting functional analogy between yeast Kex 2p and the cellular protease responsible for the maturation of HIV- 1 envelope Glycoproteins in infected human cells.


Influenza virus hemagglutinin with multibasic cleavage site is activated by furin, a subtilisin‐like endoprotease.
Peptidyl chloroalkylketones containing the R‐X‐K/R‐R motif specifically bind to the catalytic site of furin and are therefore potent inhibitors of hemagglutinin cleavage and fusion activity.
Mutational analysis of the human immunodeficiency virus type 1 env gene product proteolytic cleavage site
The structural requirements for proteolytic cleavage of the human immunodeficiency virus type 1 env gene product, gp160, to gp120 and gp41 have been assessed by specific mutagenesis of the sequence
Biosynthesis, cleavage, and degradation of the human immunodeficiency virus 1 envelope glycoprotein gp160.
The synthesis and processing of the human immunodeficiency virus 1 (HIV-1) envelope precursor glycoprotein gp 160 was studied in an infected CD4+ lymphocytic cell line and results indicate that intracellular cleavage of gp160 determines the intrACEllular transport and survival of the envelope glycoproteins necessary to produce infectious virus.
Biosynthesis and processing of human immunodeficiency virus type 1 envelope glycoproteins: effects of monensin on glycosylation and transport
The infectivity of human immunodeficiency virus type 1 was also reduced by monensin treatment, a decrease that may be due to incompletely glycosylated forms of gp120 that have a lower affinity for the CD4 receptor.
Oligomeric structure of the human immunodeficiency virus type 1 envelope glycoprotein.
  • P. Earl, R. Doms, B. Moss
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1990
It is shown that gp160 is synthesized as a monomer and subsequently forms stable homodimers and the molecule remains dimeric after cleavage to gp120/gp41 but is less stable to detergent solubilization and centrifugation.