Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.
In vitro effects of anti-HIV immunotoxins directed against multiple epitopes on HIV type 1 envelope glycoprotein 160.
AIDS Res Hum Retroviruses. 1996 Jul 20;12(11):1041-51. Unique Identifier : AIDSLINE MED/96424759 Pincus SH; Wehrly K; Cole R; Fang H; Lewis GK; McClure J; Conley AJ; Wahren B; Posner MR; Notkins AL; Tilley SA; Pinter A; Eiden L; Teintze M; Dorward D; Tolstikov VV; Laboratory of Microbial Structure and Function, Rocky Mountain; Laboratories, National Institute of Allergy and Infectious; Diseases, Hamilton, Montana 59840, USA.
Abstract:
We have used a panel of anti-gp160 MAbs to construct anti-HIV immunotoxins by coupling antibodies to ricin A chain (RAC). The ability of the immunotoxins to kill HIV-1-infected cells and halt the spread of infection was tested in tissue culture on persistently and acutely infected cell lines and primary lymphocyte cultures stimulated with phytohemagglutinin (PHA blasts). Laboratory strains and clinical isolates of HIV both were tested. The constitution and antigen-binding capacity of the immunotoxins were confirmed by ELISA and indirect immunofluorescence. Immunotoxins that bind epitopes exposed on the cell surface effectively killed persistently infected cells, although killing was not directly proportional to binding of immunotoxin to cell. The activity of anti-gp41, but not anti-gp120, immunotoxins was markedly enhanced in the presence of soluble CD4 or peptides corresponding to the CDR3 region of CD4. CD4-mediated enhancement of anti-gp41 immunotoxin activity was observed for laboratory strains neutralized by sCD4 and for clinical isolates that were resistant to neutralization by sCD4. Immunotoxin action was potentiated by brefeldin A, bafilomycin A1, cortisone, and an amphipathic fusion peptide, but not by cytochalasin D, nocodazol, monodansyl cadaverine, or trans-retinoic acid. Anti-HIV immunotoxins are useful tool with which to study the functional expression of gp120/gp41 antigens on the surface of HIV-infected cells, as well as potential AIDS therapeutics. Because these studies relate to the accessibility of viral antigens to antibody-mediated attack, these studies also have relevance for vaccine development.
Keywords: Antibiotics, Antifungal/PHARMACOLOGY Antibiotics, Macrolide/PHARMACOLOGY Cell Line Cortisone/PHARMACOLOGY Cyclopentanes/PHARMACOLOGY Cytochalasin D/METABOLISM Enzyme-Linked Immunosorbent Assay Epitopes/*IMMUNOLOGY Human HIV Envelope Protein gp160/*IMMUNOLOGY HIV Envelope Protein gp41/IMMUNOLOGY HIV-1/DRUG EFFECTS/*IMMUNOLOGY Immunotoxins/*PHARMACOLOGY Microscopy, Electron, Scanning Nocodazole/PHARMACOLOGY Phytohemagglutinins/IMMUNOLOGY Support, U.S. Gov't, P.H.S. JOURNAL ARTICLE 970330
M9731493
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.
Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.
