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

Dzung H. Nguyen, Zhaohao Liao, J. Thomas Buckley, James Hildreth

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 incorporate Thy-1 and other GPI-anchored proteins into its membrane. Here, we show that aerolysin is capable of neutralizing HIV-1 in a dose-dependent manner and that neutralization depends upon the presence of these proteins in the viral 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-anchored 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 neutralization to occur. These findings represent the first evidence that a pathogenic human virus can be neutralized by a bacterial toxin.

Original languageEnglish (US)
Pages (from-to)659-666
Number of pages8
JournalMolecular Microbiology
Volume33
Issue number3
DOIs
StatePublished - 1999
Externally publishedYes

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Glycosylphosphatidylinositols
HIV-1
Viruses
Proteins
Viral Envelope Proteins
Phosphoinositide Phospholipase C
Bacterial Toxins
Aeromonas
Membranes
Permeability
T-Lymphocytes
Amino Acids
Cell Line
aerolysin

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

Cite this

The channel-forming toxin aerolysin neutralizes human immunodeficiency virus type 1. / Nguyen, Dzung H.; Liao, Zhaohao; Buckley, J. Thomas; Hildreth, James.

In: Molecular Microbiology, Vol. 33, No. 3, 1999, p. 659-666.

Research output: Contribution to journalArticle

Nguyen, Dzung H. ; Liao, Zhaohao ; Buckley, J. Thomas ; Hildreth, James. / The channel-forming toxin aerolysin neutralizes human immunodeficiency virus type 1. In: Molecular Microbiology. 1999 ; Vol. 33, No. 3. pp. 659-666.
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