Heparin-binding domain of human fibronectin binds HIV-1 gp120/160 and reduces virus infectivity.
In vitro experiments indicate that components of the host present in body fluids may prevent the attachment of human immunodeficiency virus type 1 (HIV-1) to target cells. Fibronectin (Fn), a dimeric 440-kDa extracellular matrix adhesion protein, is secreted by mesenchymal cells and assembled into insoluble matrices. Fn exerts important effects on cell growth and differentiation through a number of discrete functional domains. Several microorganisms are known to bind Fn. We show that, under physiological conditions, HIV-1 gp120 and gp160 are capable of binding plasma and cellular Fn as well as laminin and vitronectin. Experiments were set up to analyze in detail the binding of HIV gp120 and gp160 to Fn. The gp120 and gp160 specifically recognize the C-terminal heparin-binding domain of Fn (Fn-CTHBD) with a calculated KD of 2.8 x 10(-7) M for gp160. Binding of gp160 to Fn-CTHBD is a saturable and specific process that is blocked by antibodies to Fn-CTHBD and by heparin and is inhibited to a minor extent by heparan sulfate and dextran sulfate. These observations suggest that gp120/160 specifically recognize the III15 repeat within Fn-CTHBD. Intact Fn and Fn-CTHBD strongly inhibit the interaction of gp120/160 with soluble CD4 and, under low serum conditions, are capable of neutralizing the infectivity of HIV-1 for CD4-positive T cells. Thus, Fn that is present in plasma and mucinous secretions may well affect HIV infectivity and virus distribution in vivo.
Bozzini
S
S
Department of Clinical and Biological Sciences, University of Pavia, Varese, Italy.
Falcone
V
V
Conaldi
P G
PG
Visai
L
L
Biancone
L
L
Dolei
A
A
Toniolo
A
A
Speziale
P
P
D000906:Antibodies / Q000494:pharmacology; D015153:Blotting, Western; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000378:metabolism; D005353:Fibronectins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D019302:HIV Envelope Protein gp160 / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism* / Q000472:pathogenicity; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D007797:Laminin / Q000378:metabolism; D009961:Orosomucoid / Q000378:metabolism; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000821:virology; D019096:Vitronectin / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism
D000906:Antibodies; D015704:CD4 Antigens; D005353:Fibronectins; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D007797:Laminin; D009961:Orosomucoid; D019096:Vitronectin; D000509:alpha-Fetoproteins; D005340:Fibrinogen; D006493:Heparin