Abstract
DC-SIGN, a C-type lectin receptor expressed in dendritic cells (DCs), has been identified as a receptor for human immunodeficiency virus type 1, hepatitis C virus, Ebola virus, cytomegalovirus, dengue virus, and the SARS coronavirus. We used H5N1 pseudotyped and reverse-genetics (RG) virus particles to study their ability to bind with DC-SIGN. Electronic microscopy and functional assay results indicate that pseudotyped viruses containing both HA and NA proteins express hemagglutination and are capable of infecting cells expressing alpha-2,3-linked sialic acid receptors. Results from a capture assay show that DC-SIGN-expressing cells (including B-THP-1/DC-SIGN and T-THP-1/DC-SIGN) and peripheral blood dendritic cells are capable of transferring H5N1 pseudotyped and RG virus particles to target cells; this action can be blocked by anti-DC-SIGN monoclonal antibodies. In summary, (a) DC-SIGN acts as a capture or attachment molecule for avian H5N1 virus, and (b) DC-SIGN mediates infections in cis and in trans.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal
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Cell Adhesion Molecules / immunology*
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Cell Line
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Dendritic Cells / immunology
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Dendritic Cells / virology
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Dogs
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Hemagglutination, Viral / immunology
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Hemagglutinin Glycoproteins, Influenza Virus / chemistry
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Hemagglutinin Glycoproteins, Influenza Virus / immunology
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Humans
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Influenza A Virus, H5N1 Subtype / genetics
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Influenza A Virus, H5N1 Subtype / immunology*
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Influenza in Birds / immunology*
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Influenza in Birds / transmission
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Influenza, Human / immunology*
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Influenza, Human / transmission
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Lectins, C-Type / immunology*
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Neuraminidase / immunology
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Poultry / immunology
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Poultry / virology
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Protein Conformation
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Receptors, Cell Surface / immunology*
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Viral Proteins / immunology
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Virion / genetics
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Virion / immunology
Substances
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Antibodies, Monoclonal
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Cell Adhesion Molecules
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DC-specific ICAM-3 grabbing nonintegrin
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Hemagglutinin Glycoproteins, Influenza Virus
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Lectins, C-Type
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Receptors, Cell Surface
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Viral Proteins
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hemagglutinin, avian influenza A virus
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sialic acid receptor
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NA protein, influenza A virus
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Neuraminidase