The channel-forming toxin aerolysin neutralizes human immunodeficiency virus type 1

Aerolysin is a channel-forming toxin secreted by Aeromonas spp. that binds to glycosyl phosphatidylinositol (GPI)-anchored proteins, such as Thy-1, on sensitive target cells. Receptor binding is followed first by oligomerizat ion of the toxin and then by insertion of the oligomers into the membrane t o form stable channels that disrupt the permeability barrier. Human immunod eficiency virus type 1 (HIV-1) produced from T cells is known to incorporat e Thy-1 and other GPI-anchored proteins into its membrane, Here, we show th at aerolysin is capable of neutralizing HIV-1 in a dose-dependent manner an d that neutralization depends upon the presence of these proteins in the vi ral envelope, Pretreatment with phosphatidylinositol-specific phospholipase C to remove GPI-anchored proteins greatly reduced HIV-1 sensitivity to the toxin, and Virus originating from a mutant cell line that lacks GPI-anchor ed proteins was not neutralized. Aerolysin variants with single amino acid changes that prevent oligomerization or insertion of the toxin were unable to inactivate the virus, implying that channel formation is necessary for n eutralization to occur. These findings represent the first evidence that a pathogenic human virus can be neutralized by a bacterial toxin.