Stimulation of human natural interferon-α response via paramyxovirus hemagglutinin lectin-cell interaction

• Published in: Journal of molecular medicine (Berlin, Germany) Vol. 80; no. 7; pp. 443 - 451
• Main Authors: JINYANG ZENG, FOURNIER, Philippe, SCHIRRMACHER, Volker
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-07-2002
• Subjects: Adsorption; Animals; Biological and medical sciences; Cell Line; Cricetinae; Experimental viral diseases and models; Flow Cytometry; HN Protein - genetics; HN Protein - immunology; HN Protein - metabolism; Humans; Immunity, Innate - physiology; Infectious diseases; Interferon-alpha - immunology; Interferon-alpha - metabolism; Leukocytes, Mononuclear - metabolism; Medical sciences; Mutagenesis, Site-Directed; Newcastle disease virus - metabolism; Newcastle disease virus - radiation effects; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - metabolism; Respirovirus - immunology; Respirovirus - metabolism; Sialic Acids - metabolism; Ultraviolet Rays; Viral diseases; Cell culture; Lectin; Hemagglutinin; Alpha interferon; Pathogenesis; Natural immunity; Cell cell interaction; Stimulation; Kidney; Paramyxoviridae; Mononuclear cell; Newcastle disease virus; Enzyme; Cytokine; Rodentia; In vitro; Infection; Virus; Response; Paramyxovirinae; Mononegavirales; Vertebrata; Mammalia; Glycosidases; Animal; Exo-α-sialidase; Viral disease; Rubulavirus; Hydrolases; Genetic engineering; Molecular biology; O-Glycosidases; Hamster; Paramyxovirus
• ISSN: 0946-2716; 1432-1440
• DOI: 10.1007/s00109-002-0339-1

A lectin-carbohydrate recognition event without enzymatic function is proposed as molecular basis for an important innate immune response to enveloped viruses. It involves the hemagglutinin-neuraminidase (HN) glycoprotein of Newcastle disease virus (NDV) and sialic acid expressing cellular receptors on human natural interferon (IFN) alpha producing cells. This conclusion is based on two types of experimental evidence: (a) strong UV irradiation of NDV, which destroyed the cell binding and hemadsorption (HAd) but not the neuraminidase (NA) activity of HN, also destroyed its IFN-alpha inducing activity; (b) DNA transfectants expressing HN mutant molecules with greatly reduced NA but not HAd activity induced IFN-alpha while transfectants expressing HN mutant molecules with greatly reduced NA and HAd activity were incapabable of inducing IFN-alpha in human peripheral blood mononuclear cells. The results clarify molecular mechanisms involved in pattern recognition during innate immune responses.