Antagonism between viral infection and innate immunity at the single-cell level

Abstract

When infected with a virus, cells may secrete interferons (IFNs) that prompt nearby cells to prepare for upcoming infection. Reciprocally, viral proteins often interfere with IFN synthesis and IFN-induced signaling. We modeled the crosstalk between the propagating virus and the innate immune response using an agent-based stochastic approach. By analyzing immunofluorescence microscopy images we observed that the mutual antagonism between the respiratory syncytial virus (RSV) and infected A549 cells leads to dichotomous responses at the single-cell level and complex spatial patterns of cell signaling states. Our analysis indicates that RSV blocks innate responses at three levels: by inhibition of IRF3 activation, inhibition of IFN synthesis, and inhibition of STAT1/2 activation. In turn, proteins coded by IFN-stimulated (STAT1/2-activated) genes inhibit the synthesis of viral RNA and viral proteins. The striking consequence of these inhibitions is lack of coincidence of viral proteins and IFN expression within single cells. The model enables investigation of the impact of immunostimulatory defective viral particles and signaling network perturbations that could potentially facilitate containment or clearance of the viral infection.

PAPRECA: A parallel hybrid off-lattice kinetic Monte Carlo/molecular dynamics simulator

“…Additionally, the Stochastic Parallel PARticle Kinetic Simulator (SPPARKS) (Mitchell et al, 2023) offers solely on-lattice kMC modeling capabilities, since the only currently available off-lattice solver is a Metropolis Monte Carlo relaxation scheme. Furthermore, a wide range of on-lattice kMC packages such as kmcos (Reuter et al, 2020), PyCD (Pasumarthi, 2017), VIS-A-VIS (Grabowski & Kochanczyk, 2022), MulSKIPS (Helleboid, 2021), Kimocs (Jansson, 2016), KSOME (Nandipati, 2021), kMCpy (Deng, 2022), and Morphokinetics (Alberdi & Albi, 2018) are available in open-source software repositories.…”