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: We also examined whether the same effects were seen during the course of other RNA virus infections. Each of PIV2, PIV3, FLUAV and BUNV produce larger plaques on cells that have been engineered to either not produce or respond to IFN (Fig. 6A), and thus some cells must be secreting IFN that is inducing an anti-viral state in the surrounding uninfected cells, thereby slowing the spread of the infection. When the production of IFN was monitored using the GFP reporter in A549/pr(IFN-β).GFP cells we observed that as seen for PIV5, the cells surrounding infected cells in plaques in which no GFP-positive cells could be detected, were negative for MxA expression (Fig. 6B), suggesting that no cells within these plaques had yet been activated to produce IFN. In contrast, the uninfected cells surrounding plaques containing at least one GFP-positive cell were positive for MxA (Fig. 6B). The fact that for all the viruses studied induction of MxA correlated with the presence of at least one GFP-positive cell within the developing plaque confirmed our previous conclusions that expression of GFP was a reliable marker to identify cells that were likely to have produced IFN. It should be noted that whilst the IFN-β promoter must be activated to induce GFP expression, the lack of GFP expression in infected cells could also be a consequence of post-transcriptional regulation brought about by viral antagonists such as the NS1 protein of FLUAV interfering with the processing and export of cellular mRNAs from the nucleus to the cytoplasm. Nevertheless, these results strongly suggest that only a limited number of cells infected with negative-sense RNA viruses produce the IFN that establishes an anti-viral state in the uninfected cells surrounding the developing plaque, thereby slowing the spread of the infection.
Affiliation: School of Biology, Centre for Biomolecular Sciences, BMS Building, North Haugh, University of St. Andrews, St. Andrews, Fife, KY16 9ST, UK.