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Evaluating the Within-Host Dynamics of Ranavirus Infection with Mechanistic Disease Models and Experimental Data

1
School of Informatics, Computing and Cyber Systems, Northern Arizona University, Flagstaff, AZ 86011, USA
2
Department of Population Medicine, University of Guelph, Guelph, ON N1G 2W1, Canada
3
School of Biological Sciences, Washington State University, Pullman, WA 99163, USA
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(5), 396; https://doi.org/10.3390/v11050396
Received: 28 February 2019 / Revised: 23 April 2019 / Accepted: 25 April 2019 / Published: 27 April 2019
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Abstract

Mechanistic models are critical for our understanding of both within-host dynamics (i.e., pathogen replication and immune system processes) and among-host dynamics (i.e., transmission). Within-host models, however, are not often fit to experimental data, which can serve as a robust method of hypothesis testing and hypothesis generation. In this study, we use mechanistic models and empirical, time-series data of viral titer to better understand the replication of ranaviruses within their amphibian hosts and the immune dynamics that limit viral replication. Specifically, we fit a suite of potential models to our data, where each model represents a hypothesis about the interactions between viral replication and immune defense. Through formal model comparison, we find a parsimonious model that captures key features of our time-series data: The viral titer rises and falls through time, likely due to an immune system response, and that the initial viral dosage affects both the peak viral titer and the timing of the peak. Importantly, our model makes several predictions, including the existence of long-term viral infections, which can be validated in future studies. View Full-Text
Keywords: amphibian; Ranavirus; frog virus 3; mathematical models; Bayesian inference amphibian; Ranavirus; frog virus 3; mathematical models; Bayesian inference
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Mihaljevic, J.R.; Greer, A.L.; Brunner, J.L. Evaluating the Within-Host Dynamics of Ranavirus Infection with Mechanistic Disease Models and Experimental Data. Viruses 2019, 11, 396.

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