Comparative functional role of PC7 and furin in the processing of the HIV envelope glycoprotein gp160.
The intracellular proteolytic processing of HIV envelope glycoprotein gp160 into gp120/gp41 is an essential step for virus infectivity. Several convertases, belonging to the pro-protein convertase family, have been proposed as candidate gp160 processing enzymes. Here we demonstrate using RT-PCR that resting human T4 lymphocytes weakly express PC7, furin, and PC5 mRNA whereas lymphocytes activated under conditions favoring HIV replication express 5-10-fold higher levels of furin and PC7. In this report, we examined the capability of the newly cloned convertase PC7 to cleave gp160 into gp120/gp41 and compared it to furin. This was carried out in a cell-based assay whereby both gp160 and the cognate convertase were co-expressed in the constitutively secreting BSC40 cells and in the regulated AtT20 cells, as well as using two in vitro assays which examined the cleavage of gp160 or of a synthetic peptide spanning the cleavage site. The data demonstrate that PC7 can cleave specifically and in a cell-type specific manner gp160 into gp120gp41, suggesting that both furin and PC7 are so far the major PC-like candidate gp160 convertase in T4 lymphocytes.
Decroly
E
E
J.A. DeSève Laboratory of Biochemical Neuroendocrinology, University of Montreal, QC, Canada.
Benjannet
S
S
Savaria
D
D
Seidah
N G
NG
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D045683:Furin; D006678:HIV / Q000502:physiology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D019302:HIV Envelope Protein gp160 / Q000378:metabolism*; D015700:HIV Envelope Protein gp41 / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013381:Subtilisins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C099101:PCSK7 protein, human; C490930:Pcsk7 protein, mouse; C490931:Pcsk7 protein, rat; D013381:Subtilisins; D045683:Furin