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-7 hours 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.

Analysis of tick-borne encephalitis virus-induced host responses in human cells of neuronal origin and interferon-mediated protection

“…of 5. A549 cells were used as controls, given their wide use in type I IFN studies (for example [31][32][33][34]). Cells were incubated for 5 days until a virus-induced cytopathic effect (CPE) was observed in the control wells.…”

The role of spatial structure in the evolution of viral innate immunity evasion: A diffusion-reaction cellular automaton model

“…Because IFN is smaller and hence diffuses faster than virions, immunization can reach larger areas than infection, even if cells release virions faster than IFN. Delayed but effective innate immune responses capable of successfully arresting virus progression by producing a ring of immunized cells around infection foci have been experimentally shown previously using IFN-stimulating virus variants [24].…”

“…Based on known dynamics [24][25][26], though, we initially assumed that virion release preceded IFN secretion (N Eπ � 0). We also incorporated the observation that uninfected cells respond to IFN in a dose-dependent manner [5,27] and become immunized (N R ), but do not produce IFN themselves [28].…”

Quantitative profiling of innate immune activation by viral infection in single cells

“…It is an open question how this balance of activation and viral protein production plays out within spreading infections. How the race between the viral progeny and defensive cytokines plays out will ultimately depend not only on their production and release kinetics, but also their physical transport to neighboring susceptible cells, reflecting an integration of biological and physical processes [43,44, 60–62]. …”