AEGiS-11IAC: Comparative processing of human immunodeficiency virus HIV-1 envelope glycoprotein gp160 by the mammalian subtilisin/kexin-like convertases.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Comparative processing of human immunodeficiency virus HIV-1 envelope glycoprotein gp160 by the mammalian subtilisin/kexin-like convertases.

Int Conf AIDS 1996 Jul 7-12; 11:6 (abstract no. We.A.155)
Decroly E, Ruysschaert JM, Seidah NG; IRCM, Montreal, Canada.

OBJECTIVE: Intracellular proteolytic processing of Human Immunodeficiency Virus (HIV) envelope glycoprotein precursor (gp160) into gp120 and gp41 is an essential step for virus infectivity and fusion process. Cellular proteolytic maturation requires highly conserved basic amino acid sequences also identified in the maturation process of hormonal precursors, neuropeptides and receptors. The Subtilisin-like serine proteases family called "prohormones convertases" (Furin, PC1/PC3, PC2, PACE4, PC4, PC5/PC6, PC7) could be involved in the virus processing. Recently, Garten's group provided evidence that coexpression of gp160 and furin enhances the fraction of gp160 cleaved into gp120 and gp41 (1). However, it is not clear whether other convertases are implicated in this proteolytic maturation (2). The aim of the present study was to identify, in vitro, the convertases which can activate gp160 and to test HIV-sensitive CD4+ cells for the presence of active subtilisin-like enzymes.

METHODS: Northern Blot, enzymatic cleavage

RESULTS: In this work, we demonstrated that 5 (PC1, Furin, PACE4, PC5 and PC6B) of the seven known convertases cleave in vitro gp160 into gp120 and gp41. Finally, we detected by Northern blot the presence of mRNA convertases in 3 different CD4+ lymphocyte cell lines.

CONCLUSIONS: Demonstration of gp160 specific cleavage by 5 convertases of the subtilisin-like family and the presence of several mRNA convertases within lymphocyte cells lines suggest that furin, but also other subtilisin-like convertases, may participate in gp160 maturation. 1. Hallenberg S., Bosch V., Angliker H., Shaw E., Klen H-D. and Garten W. (1993) Nature 360, 358-361. 2. Decroly E., Vandenbranden M., Ruysschaert J-M., Cogniaux J., Jacob G., Howard S., Marshall G., Kompelli A., Basak A., Jean F., Lazure C., Benjannet S., Chretien M., Day R. and Seidah N. (1994) J. Biol. Chem. 269, 12240-12247.

Keywords: AEGIS, HIV Envelope Protein gp160, Subtilisins, Subtilisin, HIV, Serine Endopeptidases, HIV Envelope Protein gp120, HIV Envelope Protein gp41, CD4-Positive T-Lymphocytes, HIV Antigens, Cell Line, Oligopeptides, furin, kexin, tetrapeptide carbamate, Human, In Vitro, ICA11

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