Identification of Conserved Residues in the Human Immunodeficiency Virus Type 1 Principal Neutralizing Determinant That Are Involved in Fusion

The principal neutralizing determinant of the human immunodeficiency virus type 1 (HIV-1) is located within the V3 loop of the surface glycoprotein gp 120. Recently a mutational approach was used to demonstrate that the tip of the V3 loop is involved in cell fusion mediated by the HIV-1 envelope glycoproteins. Here these results are extended by introducing seven additional single amino acid mutations in the V3 loop. Mutations at highly conserved amino acids in the left stem, tip, and right stem of the V3 loop blocked or greatly reduced cell fusion without affecting envelope glycoprotein processing, transport, or binding to the CD4 receptor molecule. This study further characterizes the involvement of the V3 loop in cell fusion mediated by the HIV-1 envelope glycoproteins and identifies residues involved in the fusion reaction.