Document Detail


Construction and enhanced cytotoxicity of a [cyanovirin-N]-[Pseudomonas exotoxin] conjugate against human immunodeficiency virus-infected cells.
MedLine Citation:
PMID:  9367864     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cyanovirin-N (CV-N) is a novel 11-kDa anti-HIV(human immunodeficiency virus) protein that binds with high affinity to the viral envelope glycoprotein gp120. In contrast to soluble CD4 and most known neutralizing antibodies that bind gp120, CV-N exerts potent anti-viral activity against primary clinical HIV isolates as well as laboratory-adapted strains of HIV. Here we describe the recombinant production, purification, and characterization of a chimeric toxin molecule, FLAG-CV-N-PE38, that contains CV-N as a gp120-targeting moiety linked to the translocation and cytotoxic domains of Pseudomonas exotoxin A. FLAG-CV-N-PE38 showed enhanced cytotoxicity to HIV-infected, gp120-expressing H9 cells compared to uninfected H9 cells. Competition experiments with free CV-N provided further support that the enhanced FLAG-CV-N-PE38-induced cytotoxicity was due to interactions of the CV-N moiety with cell surface gp120. This study establishes the feasibility of use of CV-N as a gp120-targeting sequence for construction and experimental therapeutic investigations of unique new chimeric toxins designed to selectively destroy HIV-infected host cells.
Authors:
T Mori; R H Shoemaker; J B McMahon; R J Gulakowski; K R Gustafson; M R Boyd
Related Documents :
22716104 - Immune reconstitution in hiv+ subjects on lopinavir/ritonavir-based haart according to ...
19641744 - Tunneling nanotubes (tnt): a potential mechanism for intercellular hiv trafficking.
17565674 - Differential in vitro inhibitory activity against hiv-1 of alpha-(1-3)- and alpha-(1-6)...
22301414 - Pathogen prevalence may determine maintenance of antigen-specific t-cell responses in h...
18663044 - Diagnostic yield of fine-needle aspiration cytology in hiv-infected patients with lymph...
17331464 - Hcv core protein induces hepatic lipid accumulation by activating srebp1 and ppargamma.
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  239     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  1997 Oct 
Date Detail:
Created Date:  1997-12-12     Completed Date:  1997-12-12     Revised Date:  2006-05-01    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  884-8     Citation Subset:  IM; X    
Affiliation:
Laboratory of Drug Discovery Research and Development, National Cancer Institute, Frederick, Maryland 21702-1201, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
ADP Ribose Transferases*
Anti-HIV Agents / chemical synthesis*,  chemistry,  toxicity
Bacterial Proteins*
Bacterial Toxins*
Carrier Proteins / chemistry,  genetics*,  toxicity
Enzyme-Linked Immunosorbent Assay
Exotoxins / chemistry,  genetics*,  toxicity
HIV Envelope Protein gp120 / biosynthesis
HIV-1 / drug effects*
Humans
Leukemia
Plasmids
Pseudomonas aeruginosa / genetics*
Recombinant Fusion Proteins / chemical synthesis*,  chemistry,  toxicity*
Tumor Cells, Cultured
Virulence Factors*
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Bacterial Proteins; 0/Bacterial Toxins; 0/Carrier Proteins; 0/Exotoxins; 0/HIV Envelope Protein gp120; 0/Recombinant Fusion Proteins; 0/Virulence Factors; 184539-38-6/cyanovirin N; EC 2.4.2.-/ADP Ribose Transferases; EC 2.4.2.31/toxA protein, Pseudomonas aeruginosa

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Novel splicing of an IGF2 polymorphic region in human adrenocortical carcinomas.
Next Document:  Adenovirus-mediated gene transfer of C-type natriuretic peptide causes G1 growth inhibition of cultu...