L. Chernomordik et al., AN AMPHIPATHIC PEPTIDE FROM THE C-TERMINAL REGION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS ENVELOPE GLYCOPROTEIN CAUSES PORE FORMATION IN MEMBRANES, Journal of virology, 68(11), 1994, pp. 7115-7123
The peptide fragment of the carboxy-terminal region of the human immun
odeficiency virus (HIV) transmembrane protein (gp41) has been implicat
ed in T-cell death. This positively charged, amphipathic helix (amino
acids 828 to 848) of the envelope protein is located within virions or
cytoplasm. We studied the interaction of the isolated, synthetic amph
ipathic helix of gp41 with planar phospholipid bilayer membranes and w
ith Sf9 cells using voltage clamp, potentiodynamic, and single-cell re
cording techniques. We found that the peptide binds strongly to planar
membranes, especially to the negatively charged phosphatidylserine bi
layer. In the presence of micromolar concentrations of peptide suffici
ent to make its surface densities comparable,vith those of envelope gl
ycoprotein molecules in HIV virions, an increase in bilayer conductanc
e and a decrease in bilayer stability were observed, showing pore form
ation in the planar lipid bilayers. These pores were permeable to both
monovalent and divalent cations, as well as to chloride. The exposure
of the inner leaflet of cell membranes to even 25 nM peptide increase
d membrane conductance. We suggest that the carboxy terminal fragment
of the HIV type 1 envelope protein may interact,vith the cell membrane
of infected T cells to create lipidic pores which increase membrane p
ermeability, leading to sodium and calcium flux into cells, osmotic sw
elling, and T-cell necrosis or apoptosis.