Identification of nucleolin as a cellular receptor for human respiratory syncytial virus
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- 14 August 2011
- journal article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 17 (9), 1132-1135
- https://doi.org/10.1038/nm.2444
Abstract
Human respiratory syncytial virus (RSV) causes a large burden of disease worldwide. There is no effective vaccine or therapy, and the use of passive immunoprophylaxis with RSV-specific antibodies is limited to high-risk patients. The cellular receptor (or receptors) required for viral entry and replication has yet to be described; its identification will improve understanding of the pathogenesis of infection and provide a target for the development of novel antiviral interventions. Here we show that RSV interacts with host-cell nucleolin via the viral fusion envelope glycoprotein and binds specifically to nucleolin at the apical cell surface in vitro. We observed decreased RSV infection in vitro in neutralization experiments using nucleolin-specific antibodies before viral inoculation, in competition experiments in which virus was incubated with soluble nucleolin before inoculation of cells, and upon RNA interference (RNAi) to silence cellular nucleolin expression. Transfection of nonpermissive Spodoptera frugiperda Sf9 insect cells with human nucleolin conferred susceptibility to RSV infection. RNAi-mediated knockdown of lung nucleolin was associated with a significant reduction in RSV infection in mice (P = 0.0004), confirming that nucleolin is a functional RSV receptor in vivo.Keywords
This publication has 33 references indexed in Scilit:
- Neutralization of Human Respiratory Syncytial Virus Infectivity by Antibodies and Low-Molecular-Weight Compounds Targeted against the Fusion GlycoproteinJournal of Virology, 2010
- A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virusProceedings of the National Academy of Sciences of the United States of America, 2010
- Emerging drugs for respiratory syncytial virus infectionEmerging Drugs, 2009
- Cell-surface nucleolin is a signal transducing P-selectin binding protein for human colon carcinoma cellsExperimental Cell Research, 2008
- Viral and Host Factors in Human Respiratory Syncytial Virus PathogenesisJournal of Virology, 2008
- Identification of Linear Heparin-Binding Peptides Derived from Human Respiratory Syncytial Virus Fusion Glycoprotein That Inhibit InfectivityJournal of Virology, 2007
- Transcriptional regulation by Modulo integrates meiosis and spermatid differentiation in male germ lineProceedings of the National Academy of Sciences of the United States of America, 2006
- Pleiotrophin inhibits HIV infection by binding the cell surface‐expressed nucleolinThe FEBS Journal, 2005
- Blocking Intercellular Adhesion Molecule-1 on Human Epithelial Cells Decreases Respiratory Syncytial Virus InfectionBiochemical and Biophysical Research Communications, 2001
- Heparin-dependent attachment ofrespiratory syncytial virus (RSV) to host cellsArchiv für die gesamte Virusforschung, 1997