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M94A0331.TXT
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Document 0331
DOCN M94A0331
TI Liposome targeting to human immunodeficiency virus type 1-infected cells
via recombinant soluble CD4 and CD4 immunoadhesin (CD4-IgG).
DT 9412
AU Flasher D; Konopka K; Chamow SM; Dazin P; Ashkenazi A; Pretzer E;
Duzgunes N; Department of Microbiology, School of Dentistry, University
of; the Pacific, San Francisco, CA 94115-2399.
SO Biochim Biophys Acta. 1994 Aug 24;1194(1):185-96. Unique Identifier :
AIDSLINE MED/94355361
AB HIV-infected cells producing virions express the viral envelope
glycoprotein gp120/gp41 on their surface. We examined whether liposomes
coupled to recombinant soluble CD4 (sCD4, the ectodomain of CD4 which
binds gp120 with high affinity) could specifically bind to HIV-infected
cells. sCD4 was chemically coupled by 2 different methods to liposomes
containing rhodamine-phosphatidylethanolamine in their membrane as a
fluorescent marker. In one method, sCD4 was thiolated with
N-succinimidyl acetylthioacetate (SATA) and coupled to liposomes via a
maleimide-derivatised phospholipid. In the other method, the
oligosaccharides on sCD4 were coupled to a sulfhydryl-derivatised
phospholipid, utilizing the bifunctional reagent,
4-(4-N-maleimidophenyl)butyric acid hydrazide (MPBH). The association of
the liposomes with HIV-1-infected or uninfected cells was examined by
flow cytometry. CD4-coupled liposomes associated specifically to
chronically infected H9/HTLV-IIIB cells, but not to uninfected H9 cells.
CD4-coupled liposomes also associated specifically with monocytic THP-1
cells chronically infected with HIV-1 (THP-1/HIV-1IIIB). Control
liposomes without coupled CD4 did not associate significantly with any
of the cells, while free sCD4 could competitively inhibit the
association of the CD4-coupled liposomes with the infected cells. The
chimeric molecule CD4-immunoadhesin (CD4-IgG) could also be used as a
ligand to target liposomes with covalently coupled Protein A (which
binds the Fc region of the CD4-IgG) to H9/HTLV-IIIB cells. The
CD4-liposomes inhibited the infectivity of HIV-1 in A3.01 cells, and
also bound rgp120. Our results suggest that liposomes containing
antiviral or cytotoxic agents may be targeted specifically to
HIV-infected cells.
DE Antigens, CD4/IMMUNOLOGY/*PHARMACOLOGY Cell Line, Transformed
Comparative Study CD4 Immunoadhesins/*PHARMACOLOGY Drug Carriers Flow
Cytometry Human HIV Envelope Protein gp120/IMMUNOLOGY
HIV-1/IMMUNOLOGY/*PATHOGENICITY Liposomes/*CHEMISTRY/IMMUNOLOGY
Staphylococcal Protein A/PHARMACOLOGY Support, Non-U.S. Gov't Support,
U.S. Gov't, P.H.S. Virulence JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).