GP120-INDEPENDENT FUSION MEDIATED BY THE HUMAN-IMMUNODEFICIENCY-VIRUSTYPE-1 GP41 ENVELOPE GLYCOPROTEIN - A REASSESSMENT

In a natural context, membrane fusion mediated by the human immunodefi ciency virus type 1 (HIV-1) envelope glycoproteins involves both the e xterior envelope glycoprotein (gp120) and the transmembrane glycoprote in (gp41). Perez et al. (J. Virol. 66:4134-4143, 1992) reported that a mutant HIV-1 envelope glycoprotein containing only the signal peptide and carboxyl terminus of the gp120 exterior glycoprotein fused to the complete gp41 glycoprotein was properly cleaved and that the resultan t gp41 glycoprotein was able to induce the fusion of even CD4-negative cells. In the studies reported herein, mutant proteins identical or s imilar to those studied by Perez et al. lacked detectable cell fusion activity. The proteolytic processing of these proteins was very ineffi cient, and one processed product identified by Perez et al. as the aut hentic gp41 glycoprotein was shown to contain carboxyl-terminal gp120 sequences. Furthermore, no fusion activity was observed for gp41 glyco proteins exposed after shedding of the gp120 glycoprotein by soluble C D4. Thus, evidence supporting a gpl20-independent cell fusion activity for the HIV-1 gp41 glycoprotein is currently lacking.