Document 3329
 DOCN  M94A3329
 TI    Laminin and fibronectin interfere with the binding of HIV-1 gp120/160 to
       CD4.
 DT    9412
 AU    Bozzini S; Falcone V; Conaldi PG; Visai L; Dolei A; Speziale P; Toniolo
       A; Dept. of Biochemistry, University of Pavia, Italy.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):100 (abstract no. PA0018). Unique
       Identifier : AIDSLINE ICA10/94369246
 AB    OBJECTIVE: In vitro experiments indicate that not yet defined host
       components may hinder the early interactions of HIV-1 with target cells.
       We checked whether human extracellular matrix proteins could bind HIV-1
       env glycoproteins thus preventing virus-receptor interaction, or
       facilitating infection by trapping the virus in the immediate proximity
       of cell membranes. METHODS: Radiolabeled recombinant gp160, gp120 and
       gp41 were tested for their ability to bind solid phase-immobilized
       extracellular matrix proteins. Fibronectin fragments were obtained by
       trypsin/thermolysin digestion. The effect of extracellular matrix
       proteins on the interaction of env glycoproteins with CD4 was evaluated
       by radiometric or immunoenzymatic assay. RESULTS: HIV-1 gp120/160 bind
       to fibronectin, laminin and vitronectin, but not to fibrinogen, fetuin,
       alpha-1-acid glycoprotein. Both gp120 and gp160 bind to the
       heparin-binding domain of fibronectin, whereas gp160 interacts also with
       the DNA-binding domain. Western blot analysis of fibronectin fragments
       showed that gp120 and gp160 recognize selectively the intact protein and
       two 30KDa bands corresponding to the above mentioned domains. Binding to
       intact fibronectin and to the heparin-binding domain is inhibited in a
       dose-dependent manner by heparins, heparan sulphate, antibody
       recognizing the heparin-binding domain, and unlabeled viral proteins.
       The interaction of gp120/160 with fibronectin, vitronectin, laminin, and
       their fragments interfered with the binding of these env proteins to
       CD4. The gp120/160-CD4 interaction was inhibited by 50% to 75%.
       DISCUSSION AND CONCLUSION: The results indicate that gp120/160 bind to
       selected extracellular matrix proteins suggesting a potential role of
       these tissue components in modulating the early virus-cell interactions.
 DE    Antigens, CD4/*METABOLISM  Binding Sites  Cell
       Membrane/METABOLISM/MICROBIOLOGY  Fibronectins/*METABOLISM  Gene
       Products, env/METABOLISM  Human  HIV Envelope Protein gp120/METABOLISM
       HIV Envelope Protein gp41/METABOLISM  HIV-1/*METABOLISM  In Vitro
       Laminin/*METABOLISM  Protein Binding  Protein Precursors/METABOLISM
       Recombinant Proteins/METABOLISM  Support, Non-U.S. Gov't  MEETING
       ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).