Relationships between the anti-HIV V3-derived peptide SPC3 and lymphocyte membrane properties involved in virus entry: SPC3 interferes with CXCR4

Abstract SPC3 is a multiple antigen peptide derived from the V3 loop of human immunodeficiency virus (HIV) envelope (Env). It exerts a potent anti-HIV activity whereas it alters neither Env expression nor binding to CD4. Here, SPC3 binding characteristics, its subsequent intracellular fate and the fact that it inhibited SDF1α binding to the lymphocyte surface provided strong arguments to conclude that it exerts its anti-HIV activity through interference with the CXCR4 coreceptor. In contrast, it interferes with none of the other major surface proteins and mechanisms involving V3 and implicated in infection, as shown here. This work identifies the target mechanism of SPC3.