Heterocellular induction of interferon by negative-sense RNA viruses.
Bottom Line: The infection of cells by RNA viruses is associated with the recognition of virus PAMPs (pathogen-associated molecular patterns) and the production of type I interferon (IFN).Here we present data on the dynamics of IFN production and response during developing infections by paramyxoviruses, influenza A virus and bunyamwera virus.We show that only a limited number of infected cells are responsible for the production of IFN, and that this heterocellular production is a feature of the infecting virus as opposed to an intrinsic property of the cells.
Affiliation: School of Biology, Centre for Biomolecular Sciences, BMS Building, North Haugh, University of St. Andrews, St. Andrews, Fife, KY16 9ST, UK.Show MeSH
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Mentions: To follow the induction of an IFN-induced anti-viral state in cells surrounding sites of infection, A549 cells were seeded onto coverslips and infected with PIV5 at an moi of 0.001 pfu per cell (i.e. under these conditions most of the cells would not be infected at early time points). At various times post-infection (p.i.), the cells were fixed, and infected cells identified by immunofluorescence using an antibody directed against the nucleoprotein (NP) of PIV5. The cell population was also co-stained for MxA, which is an anti-viral protein induced in uninfected cells as a consequence of IFN binding to the type I IFN receptor. Two days after infection we routinely saw groups of 10–30 cells expressing viral antigen, indicative of viral replication and spread. Surprisingly, only some of these groups of cells were surrounded by a layer of cells that were positive for MxA (Fig. 1). Continued monitoring of the size of groups of infected cells showed that by 4 days p.i. all the remaining uninfected cells within the infected monolayers were positive for MxA, demonstrating that enough IFN had been secreted into the media to induce an anti-viral state in all the uninfected cells (data not shown). From these initial observations we concluded that by two days p.i., although some infected cells must have produced IFN, this was not the case for all infected cells.
Affiliation: School of Biology, Centre for Biomolecular Sciences, BMS Building, North Haugh, University of St. Andrews, St. Andrews, Fife, KY16 9ST, UK.