title: Virus-cell interactions in the induction of type 1 interferon by influenza virus in mouse spleen cells.
abstract: Inactivated influenza A virus and fixed, virus-infected cells induce type 1 interferon (IFN-alpha/beta) production in murine splenocytes. In this study, we have explored the nature of the virus-spleen cell interaction that leads to IFN-alpha/beta induction and the reason for the poor response to some virus strains. IFN-alpha/beta induction by horse serum-sensitive, but not -resistant, strains of influenza virus was inhibited in the presence of horse serum, indicating that binding of the virus to sialylated cell receptors is a necessary step in the induction process. Furthermore, influenza viruses A/PR/8/34 (H1N1) and A/WS/33 (H1N1), which were poor inducers of IFN-alpha/beta in spleen cells, were shown to have a more active neuraminidase than strains that induced higher IFN levels, and IFN-alpha/beta induction by A/PR/8/34 (H1N1) and A/WS/33 (H1N1) was restored in the presence of a neuraminidase inhibitor. Growth of virus in different cell types altered the level of IFN-alpha/beta induced in spleen cells by particular virus strains, suggesting that the nature of the carbohydrate moieties on the viral glycoproteins may also influence IFN-alpha/beta induction in this system. Consistent with this notion, treatment of egg-grown virus with periodate to oxidize viral carbohydrate greatly reduced its capacity for IFN-alpha/beta induction. Furthermore, induction of IFN-alpha/beta was inhibited in the presence of the saccharides yeast mannan and laminarin. Together these findings indicate: (i) a requirement for interaction of the virus with sialylated receptors on the IFN-producing cell; (ii) an influence of viral carbohydrate on the response; and (iii) possible involvement of a lectin-like receptor on the IFN-producing cell in the induction of IFN-alpha/beta or in regulation of this response.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia.
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Miller
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia.
authors.forename: E Margot
authors.initials: EM
authors.lastname: Anders
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D006031:Glycosylation; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007370:Interferon Type I / Q000096:biosynthesis*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009439:Neuraminidase / Q000378:metabolism; D013045:Species Specificity; D013154:Spleen / Q000166:cytology* / Q000276:immunology*
chemical_list: D007370:Interferon Type I; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid