Selective killing of HIV-infected cells by recombinant human CD4-Pseudomonas exotoxin hybrid protein

Abstract

It is projected that in the absence of effective therapy, most individuals infected with human immunodeficiency virus (HIV) will develop acquired immune deficiency syndrome (AIDS) and ultimately succumb to a combination of opportunistic microbial infections, malignancies and direct pathogenic effects of the virus. Anti-viral agents, immunomodulators, and inhibitors of specific HIV functions are being tested as potential treatments to alleviate the high morbidity and mortality. An alternative therapeutic concept involves the development of cytotoxic agents that are targeted to kill HIV-infected cells. Here we describe the purification and characterization of a recombinant protein produced in Escherichia coli that contains the HIV-binding portion of the human CD4 molecule linked to active regions of Pseudomonas exotoxin A. This hybrid protein displays selective toxicity toward cells expressing the HIV envelope glycoprotein and thus represents a promising novel therapeutic agent for the treatment of AIDS.