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).