Modelling Degradation and Replication Kinetics of the Zika Virus In Vitro Infection

Mathematical models of in vitro viral kinetics help us understand and quantify the main determinants underlying the virus-host cell interactions. We aimed to provide a numerical characterization of the Zika virus (ZIKV) in vitro infection kinetics, an arthropod-borne emerging virus that has gained public recognition due to its association with microcephaly in newborns. The mathematical model of in vitro viral infection typically assumes that degradation of extracellular infectious virus proceeds in an exponential manner, that is, each viral particle has the same probability of losing infectivity at any given time. We incubated ZIKV stock in the cell culture media and sampled with high frequency for quantification over the course of 96 h. The data showed a delay in the virus degradation in the first 24 h followed by a decline, which could not be captured by the model with exponentially distributed decay time of infectious virus. Thus, we proposed a model, in which inactivation of infectious ZIKV is gamma distributed and fit the model to the temporal measurements of infectious virus remaining in the media. The model was able to reproduce the data well and yielded the decay time of infectious ZIKV to be 40 h. We studied the in vitro ZIKV infection kinetics by conducting cell infection at two distinct multiplicity of infection and measuring viral loads over time. We fit the mathematical model of in vitro viral infection with gamma distributed degradation time of infectious virus to the viral growth data and identified the timespans and rates involved within the ZIKV-host cell interplay. Our mathematical analysis combined with the data provides a well-described example of non-exponential viral decay dynamics and presents numerical characterization of in vitro infection with ZIKV.