title: Rapid induction and persistence of paracrine-induced cellular antiviral states arrest viral infection spread in A549 cells.
abstract: The virus/host interaction is a complex interplay between pro- and anti-viral factors that ultimately determines the spread or halt of virus infections in tissues. This interplay develops over multiple rounds of infection. The purpose of this study was to determine how cellular-level processes combine to impact the spatial spread of infection. We measured the kinetics of virus replication (VSV), antiviral paracrine signal upregulation and secretion, spatial spread of virus and paracrine antiviral signaling, and inhibition of virus production in antiviral-exposed A549 human lung epithelial cells. We found that initially infected cells released antiviral signals 4-to-7h following production of virus. However, the subsequent rapid dissemination of signal and fast induction of a robust and persistent antiviral state ultimately led to a suppression of infection spread. This work shows how cellular responses to infection and activation of antiviral responses can integrate to ultimately control infection spread across host cell populations.
authors.affiliation: Systems Biology Theme, Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA; Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Voigt
authors.affiliation: Systems Biology Theme, Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA; Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Swick
authors.affiliation: Systems Biology Theme, Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA; Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: john.yin@wisc.edu.
authors.forename: John
authors.initials: J
authors.lastname: Yin
mesh_terms: D000072283:A549 Cells; D000998:Antiviral Agents / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D019899:Paracrine Communication; D018406:Virus Physiological Phenomena; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D016207:Cytokines
keywords: A549 cells; Antiviral state; Infection spread; Interferon; Paracrine signaling; Virus spread