Cytotoxicity to HIV-infected cells of a Shiga toxin-CD4 fusion protein. NLM AIDSLINE Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.

Click here to return to AIDSLINE main menu
DonateNow
Print this Article


Cytotoxicity to HIV-infected cells of a Shiga toxin-CD4 fusion protein.

Abstr Gen Meet Am Soc Microbiol. 1993;93:43 (abstract no. B-96). Unique Identifier : AIDSLINE ASM93/93291808
al-Jaufy AY; Haddad JE; Jackson MP; Wayne State Univ. Medical School, Detroit, MI.

Abstract: Shiga toxin (STX), a cytotoxin produced by Shigella dysenteriae 1, is targeted to a specific glycolipid receptor on susceptible cells by its B subunit. STX enters the cell by receptor mediated endocytosis and the enzymatic (A) subunit is translocated to the ribosomes where it inhibits protein synthesis. The STX A polypeptide was genetically fused to the human CD4 molecule, which is the T cell receptor for the human immunodeficiency virus (HIV). This strategy eliminated the STX B subunit and directed the hybrid toxin to cells expressing the HIV surface glycoprotein gp120. A crude preparation containing this hybrid toxin killed the HIV-infected T cells 8E5 but was not cytotoxic toward the uninfected parental cell line A3.01. This cytotoxic activity was specifically inhibited by a monoclonal antibody which has been previously shown to block the interaction between CD4 and gp120. The StxA/CD4 hybrid toxin can be used to investigate the uptake and delivery of the enzymatic subunit to otherwise resistant cells and identify StxA domains which are required for translocation and activity.
Keywords: Antibodies, Monoclonal/PHARMACOLOGY Antigens, CD4 Bacterial Toxins/*TOXICITY Cell Death/*DRUG EFFECTS Cell Line Human HIV/*PHYSIOLOGY Recombinant Fusion Proteins/TOXICITY Shigella dysenteriae T-Lymphocytes ABSTRACTKWDantibodies,monoclonal/pharmacologyantigens,cd4bacterialtoxins/KWDtoxicitycelldeath/KWDdrugeffectscelllinehumanhiv/KWDphysiologyrecombinantfusionproteins/toxicityshigelladysenteriaet-lymphocytesabstract
930930
M9391163

Copyright © 1993 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1993. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1993. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .