Back to Search
Start Over
Heparin-binding domain of human fibronectin binds HIV-1 gp120/160 and reduces virus infectivity.
- Source :
-
Journal of medical virology [J Med Virol] 1998 Jan; Vol. 54 (1), pp. 44-53. - Publication Year :
- 1998
-
Abstract
- 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.
- Subjects :
- Antibodies pharmacology
Blotting, Western
CD4 Antigens metabolism
Cells, Cultured
Dose-Response Relationship, Drug
Fibrinogen metabolism
Fibronectins chemistry
Fibronectins immunology
Fibronectins pharmacology
HIV-1 drug effects
HIV-1 pathogenicity
Heparin pharmacology
Humans
Kinetics
Laminin metabolism
Orosomucoid metabolism
Substrate Specificity
T-Lymphocytes virology
Vitronectin metabolism
alpha-Fetoproteins metabolism
Fibronectins metabolism
HIV Envelope Protein gp120 metabolism
HIV Envelope Protein gp160 metabolism
HIV-1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0146-6615
- Volume :
- 54
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of medical virology
- Publication Type :
- Academic Journal
- Accession number :
- 9443108
- Full Text :
- https://doi.org/10.1002/(sici)1096-9071(199801)54:1<44::aid-jmv7>3.0.co;2-p