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. 1994 Mar;62(3):956–960. doi: 10.1128/iai.62.3.956-960.1994

Cytotoxicity of a shiga toxin A subunit-CD4 fusion protein to human immunodeficiency virus-infected cells.

A Y al-Jaufy 1, J E Haddad 1, S R King 1, R A McPhee 1, M P Jackson 1
PMCID: PMC186209  PMID: 8112869

Abstract

Shiga toxin (STX) is a ribosome-inactivating cytotoxin produced by Shigella dysenteriae serotype 1. The enzymatic domain of the STX A polypeptide has been defined by introducing amino- and carboxy-terminal deletions in the polypeptide and assessing activity in a cell-free translation system. Three recombinant forms of StxA which possess enzymatic activity were genetically fused to a 165-amino-acid polypeptide derived from CD4, the cellular receptor for human immunodeficiency virus type 1 (HIV-1). This strategy eliminated the STX receptor-binding subunit and directed the hybrid toxins to cells expressing the HIV-1 surface glycoprotein gp120. A bacterial lysate containing these toxin chimeras killed the HIV-1-infected T-cell line 8E5 but was not cytotoxic toward the uninfected parental cell line A3.01. This cytotoxic activity was specifically inhibited by monoclonal antibodies which block the interaction between CD4 and gp120. These StxA-CD4 hybrids add to the repertoire of recombinant fusion proteins which possess the capacity to selectively kill HIV-1-infected T cells.

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Selected References

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