Influenza A virus entry into cells lacking sialylated N-glycans
- 23 April 2012
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 109 (19), 7457-7462
- https://doi.org/10.1073/pnas.1200987109
Abstract
Influenza A virus (IAV) enters host cells after attachment of its hemagglutinin (HA) to surface-exposed sialic acid. Sialylated N-linked glycans have been reported to be essential for IAV entry [Chu VC, Whittaker GR (2004) Proc Natl Acad Sci USA 102:18153-18158], thereby implicating the requirement for proteinaceous receptors in IAV entry. Here we show, using different N-acetylglucosaminyl transferase 1 (GnT1)-deficient cells, that N-linked sialosides can mediate, but are not required for, entry of IAV. Entry into GnT1-deficient cells was fully dependent on sialic acid. Although macropinocytic entry appeared to be affected by the absence of sialylated N-glycans, dynamin-dependent entry was not affected at all. However, binding of HA to GnT1-deficient cells and subsequent entry of IAV were reduced by the presence of serum, which could be reversed by back-transfection of a GnT1-encoding plasmid. The inhibitory effect of serum was significantly increased by inhibition of the viral receptor-destroying enzyme neuraminidase (NA). Our results indicate that decoy receptors on soluble serum factors compete with cell surface receptors for binding to HA in the absence of sialylated N-glycans at the cell surface. This competition is particularly disturbed by the additional presence of NA inhibitors, resulting in strongly reduced IAV entry. Our results indicate that the balance between HA and NA is important not only for virion release, but also for entry into cells.Keywords
This publication has 20 references indexed in Scilit:
- The cell biology of receptor-mediated virus entryThe Journal of cell biology, 2011
- Dissection of the Influenza A Virus Endocytic Routes Reveals Macropinocytosis as an Alternative Entry PathwayPLoS Pathogens, 2011
- The Epidermal Growth Factor Receptor (EGFR) Promotes Uptake of Influenza A Viruses (IAV) into Host CellsPLoS Pathogens, 2010
- Glycomics Profiling of Chinese Hamster Ovary Cell Glycosylation Mutants Reveals N-Glycans of a Novel Size and ComplexityPublished by Elsevier BV ,2010
- Human host factors required for influenza virus replicationNature, 2009
- Vesicular Stomatitis Virus Enters Cells through Vesicles Incompletely Coated with Clathrin That Depend upon Actin for InternalizationPLoS Pathogens, 2009
- Epsin 1 is a cargo-specific adaptor for the clathrin-mediated endocytosis of the influenza virusProceedings of the National Academy of Sciences of the United States of America, 2008
- Carrier Cell-based Delivery of an Oncolytic Virus Circumvents Antiviral ImmunityMolecular Therapy, 2007
- Influenza Virus Can Enter and Infect Cells in the Absence of Clathrin-Mediated EndocytosisJournal of Virology, 2002
- Functional balance between haemagglutinin and neuraminidase in influenza virus infectionsReviews in Medical Virology, 2002