Selective elimination of HIV-1-infected cells with an interleukin-2 receptor-specific cytotoxin.
Infection by human immunodeficiency virus type 1 (HIV-1) is associated with cellular activation and expression of the interleukin-2 (IL-2) receptor. A genetically engineered fusion toxin, DAB486 IL-2, that contains the enzymatic site and translocation domain of diphtheria toxin and the receptor binding domain of IL-2 specifically kills cells that express high-affinity IL-2 receptors. This toxin selectively eliminated the HIV-1-infected cells from mixed cultures of infected and uninfected cells and inhibited production of viral proteins and infectious virus. Thus, cellular activation antigens present a target for early antiviral intervention.
Finberg
R W
RW
Laboratory of Infectious Diseases, Dana-Farber Cancer Institute, Boston, MA.
Wahl
S M
SM
Allen
J B
JB
Soman
G
G
Strom
T B
TB
Murphy
J R
JR
Nichols
J C
JC
D002470:Cell Survival; D004167:Diphtheria Toxin / Q000008:administration & dosage* / Q000235:genetics; D015686:Gene Products, env / Q000378:metabolism; D015683:Gene Products, gag / Q000378:metabolism; D016655:HIV Core Protein p24; D019302:HIV Envelope Protein gp160; D015658:HIV Infections / Q000628:therapy*; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000633:toxicity; D013601:T-Lymphocytes / Q000166:cytology / Q000382:microbiology*; D014758:Viral Core Proteins / Q000378:metabolism
D004167:Diphtheria Toxin; D015686:Gene Products, env; D015683:Gene Products, gag; D016655:HIV Core Protein p24; D019302:HIV Envelope Protein gp160; D007376:Interleukin-2; D011498:Protein Precursors; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D014758:Viral Core Proteins; C059767:p55 gag precursor protein, Human immunodeficiency virus 1