Recombinant CD4-Pseudomonas exotoxin hybrid protein displays HIV-specific cytotoxicity without affecting MHC class II-dependent functions.
The present study describes several in vitro activities of CD4(178)-PE40, a recombinant protein containing a portion of human CD4 linked to active regions of Pseudomonas aeruginosa exotoxin A. Using assays for cell viability, we demonstrate that the hybrid toxin displays highly selective cytotoxicity for HIV-infected T lymphocytes. In a latently infected human T-cell line which is inducible for HIV expression, toxin sensitivity is observed only upon virus induction. At concentrations which readily kill HIV-infected T cells, CD4(178)-PE40 has no observable cytotoxic effects on uninfected human cell lines expressing surface major histocompatibility complex (MHC) Class II molecules, and does not interfere with cellular responses known to be dependent on functional association between CD4 and MHC Class II molecules.
Berger
E A
EA
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Chaudhary
V K
VK
Clouse
K A
KA
Jaraquemada
D
D
Nicholas
J A
JA
Rubino
K L
KL
Fitzgerald
D J
DJ
Pastan
I
I
Moss
B
B
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D015704:CD4 Antigens / Q000276:immunology*; D002460:Cell Line; D002470:Cell Survival; D003602:Cytotoxicity, Immunologic; D005098:Exotoxins / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006681:HLA-D Antigens; D006801:Humans; D011550:Pseudomonas aeruginosa / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D015704:CD4 Antigens; D005098:Exotoxins; D006681:HLA-D Antigens; D011994:Recombinant Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A