Document 0815 DOCN M9460815 TI Cytotoxicity of a shiga toxin A subunit-CD4 fusion protein to human immunodeficiency virus-infected cells. DT 9404 AU al-Jaufy AY; Haddad JE; King SR; McPhee RA; Jackson MP; Department of Immunology and Microbiology, Wayne State University; School of Medicine, Detroit, Michigan 48201. SO Infect Immun. 1994 Mar;62(3):956-60. Unique Identifier : AIDSLINE MED/94156493 AB 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. DE Antigens, CD4/*PHYSIOLOGY Bacterial Toxins/*TOXICITY Cell Line Cytotoxins/*TOXICITY Human HIV Envelope Protein gp120/PHYSIOLOGY HIV-1/*PHYSIOLOGY Recombinant Fusion Proteins/*TOXICITY Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).