Heparin-binding domain of human fibronectin binds HIV-1 gp120/160 and reduces virus infectivity

Journal of Medical Virology
S BozziniP Speziale

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,...Continue Reading

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Citations

Aug 3, 2005·Proceedings of the National Academy of Sciences of the United States of America·Diane MaherPeter Southern
Apr 11, 2014·The Journal of Infectious Diseases·Nadia R RoanWarner C Greene
Feb 9, 2018·Viruses·Vanessa Sue WaclechePetronela Ancuta
Aug 18, 2017·Journal of Virology·David PlotnikShiu-Lok Hu
Apr 30, 2003·The Journal of Biological Chemistry·Hung-Chi ChengBendicht U Pauli
May 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Giampaolo GrecoLynn M Schnapp
May 24, 2018·Seminars in Immunopathology·Susanne G van der GreinEsther N M Nolte-'t Hoen
Mar 8, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M C TellierL M Schnapp

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