SIV gp41 binds to membranes both in the monomeric and trimeric states: Consequences for the neuropathology and inhibition of HIV infection

The viral envelope glycoprotein gp41 mediates membrane fusion in HIV/SIV in fection. gp41 ectodomain (e-gop41, residues 27-149), which was shown to int eract with phospholipid membranes, exists in an equilibrium between the mon omeric and trimeric states. Here, we analyzed, by intrinsic Trp fluorescenc e and resonance energy transfer, whether SIV e-gp41-membrane interaction de pends on the gp41 oligomeric state. We found that both gp41 monomers and tr imers bind membranes, with the monomers' full binding being reached at subs tantially lower lipid to protein ratios. Furthermore, the different charact eristics of the Trp fluorescence of monomers and trimers enabled us to dete ct binding of each form at concentrations at which both species were presen t. CD spectroscopy revealed that the secondary structure of gp41 monomers d oes not change upon membrane binding, suggesting that membrane-bound monome ric-gp41 is a possible target for DP-178, a potent peptide inhibitor of HIV infection. The consequences of the interaction between monomeric and trime ric gp41 with membranes in HIV/SIV infection, its inhibition, and its assoc iated neuropathologies are discussed. (C) 2001 Academic Press.