A Deterministic Model for Understanding Nonlinear Viral Dynamics in Oysters.

Contamination of oysters with a variety of viruses is one key pathway to trigger outbreaks of massive oyster mortality as well as human illnesses, including gastroenteritis and hepatitis. Much effort has gone into examining the fate of viruses in contaminated oysters, yet the current state of knowledge of nonlinear virus-oyster interactions is not comprehensive because most studies have focused on a limited number of processes under a narrow range of experimental conditions. A framework is needed for describing the complex nonlinear virus-oyster interactions. Here, we introduce a mathematical model that includes key processes for viral dynamics in oysters, such as oyster filtration, viral replication, the antiviral immune response, apoptosis, autophagy, and selective accumulation. We evaluate the model performance for two groups of viruses, those that replicate in oysters (e.g., ostreid herpesvirus) and those that do not (e.g., norovirus), and show that this model simulates well the viral dynamics in oysters for both groups. The model analytically explains experimental findings and predicts how changes in different physiological processes and environmental conditions nonlinearly affect in-host viral dynamics, for example, that oysters at higher temperatures may be more resistant to infection by ostreid herpesvirus. It also provides new insight into food treatment for controlling outbreaks, for example, that depuration for reducing norovirus levels is more effective in environments where oyster filtration rates are higher. This study provides the foundation of a modeling framework to guide future experiments and numerical modeling for better prediction and management of outbreaks. The fate of viruses in contaminated oysters has received a significant amount of attention in the fields of oyster aquaculture, food quality control, and public health. However, intensive studies through laboratory experiments and observations are often conducted under a narrow range of experimental conditions and for a specific purpose in their respective fields. Given the complex interactions of various processes and nonlinear viral responses to changes in physiological and environmental conditions, a theoretical framework fully describing the viral dynamics in oysters is warranted to guide future studies from a top-down design. Here, we developed a process-based, in-host modeling framework that builds a bridge for better communications between different disciplines studying virus-oyster interactions.