Viral Infection Spreading in Cell Culture with Intracellular Regulation

Abstract

Virus plaque assays are conventionally used for the assessment of viral infections, including their virulence, and vaccine efficacy. These experiments can be modeled with reaction–diffusion equations, allowing the estimation of the speed of infection spread (related to virus virulence) and viral load (related to virus infectivity). In this work, we develop a multiscale model of infection progression that combines macroscopic characterization of virus plaque growth in cell culture with a reference model of intracellular virus replication. We determine the infection spreading speed and viral load in a model for the extracellular dynamics and the kinetics of the abundance of intracellular viral genomes and proteins. In particular, the spatial infection spreading speed increases if the rate of virus entry into the target cell increases, while the viral load can either increase or decrease depending on other model parameters. The reduction in the model under a quasi-steady state assumption for some intracellular reactions allows us to derive a family of reduced models and to compare the reference model with the previous model for the concentration of uninfected cells, infected cells, and total virus concentration. Overall, the combination of different scales in reaction–diffusion models opens up new perspectives on virus plaque growth models and their applications.

Modeling of Viral Infection with Inflammation

“…Spatial distributions of the concentrations of uninfected cells U, infected cells W, and virus V at consecutive moments of time (Figure 3) correspond to wave propagation. The wave speed 0.16 cm/h and the total viral load J(V) is 3.87 × 10 7 copy/cm 2 are in agreement with the analytical results obtained with Formulas (30) and (22). The values of parameters are indicated in the figure caption.…”

“…These results were applied for the characterization of different variants of the SARS-CoV-2 infection and of their competition [20]. The influence of the immune response on infection spreading is studied in [21] and the intracellular regulation of virus replication in [22]. Mucus motion and airway obstruction during respiratory viral infections are investigated in [23].…”

Airway obstruction in respiratory viral infections due to impaired mucociliary clearance

“…Parameter estimation for different variants of the SARS‐CoV‐2 infection allows the assessment of their virulence and infectivity in agreement with the experimental, clinical and epidemiological data 13 . The basic model of infection spreading 9,10 was further developed to study the influence of immune response, 15 virus mutation and competition, 16 intracellular regulation of virus replication 17,18 …”