Neutralization of HIV-1 by Bacterial Toxins

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 oligomerization of the toxin and then by insertion of the oligomers into the membrane to form stable channels that disrupt the permeability barrier. Human immunodeficiency virus type 1 (HIV-1) produced from T cells is known to selectively incorporate Thy-1 and other GPI-anchored proteins into its membrane. We found that aerolysin is capable of neutralizing HIV-1 in a dose dependent manner and that eutralization depends upon the presence of these proteins in the viral envelope (D.H. Nguyen, Z. Liao, J. Thomas Buckley and James E.K. Hildreth (1999) The Channel-Forming Toxin Aerolysin Neutralizes Human Immunodeficiency Virus Type 1. Molecular Microbiology 33 (3): 659-666). These findings represent the first evidence that a pathogenic human virus can be neutralized by a bacterial toxin. While there are many strategies that target viral proteins for therapeutic purposes, most of these have proven unsuccessful or unsatisfactory because of the viruses ability to mutate these structures and thereby become resistant. Because aerolysin targets non-mutable host proteins, it is very unlikely that the virus will become resistant to this mechanism of neutralization. Moreover, all virus strains should be susceptible because all viruses bud from cells by the same mechanism and likely acquire GPI-anchored host molecules. Description (Set) Proposed Use (Set) Commercial applications of aerolysin may include its use: - for the killing of whole virus in vaccine development/production; - for the purging of contaminated blood products; and - as an anti-viral agent in contraceptive creams. - Further, appropriate mutants of aerolysin with reduced toxicity may be used in vivo as an anti-viral drug. Patent (Set) WO 00/61613; 6,495,315

Patents:
US 6,495,315

Inventor(s): Hildreth, James E.

Type of Offer: Licensing



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