“Little Mouse on the Prairie”: An Analysis of the Factors Influencing the Transmission Dynamics of Enterotropic Mouse Hepatitis Virus Within Wild Mus musculus Populations

Abstract

Mouse Hepatitis Virus represents one of the most infectious and widespread murine coronaviruses found today. Although the transmission dynamics of the disease have been well-studied in the lab, little is known about how the virus operates in natural populations and the extent to which outdoor conditions alter the transmission potential of the disease. The goal of this thesis, therefore, was to investigate how key factors (such as transmission rate, population size, habitat area, seasonality, and viral transmission characteristics) alter the seroprevalence rates of MHV seen in natural populations. To do this, this thesis took the form of a tri-part analysis of MHV: 1) an analysis of the dynamics of an MHV outbreak in the wild simulated through the use of a programming application based on the SIR (susceptible --> infected --> recovered) model of infectious diseases, 2) an analysis of the effect of seasonality on the observed seroprevalences of MHV in the wild, and 3) a comparative virology analysis on the extent to which transmission rates for MHV and other murine viruses can be predicted based on a virus’ transmission route type(s), their transmission route modality (number of transmission routes), and/or their viral phylogeny. Results from these analyses highlighted that while several factors in the external environment directly contribute to MHV seroprevalence (namely, large population sizes, high transmission rates (facilitated by fecal-oral spread), and climatic conditions (primarily during the winter)), many of the variables responsible for driving MHV seroprevalence values are subtly interconnected and work in concert with the intrinsic transmission advantage afforded to MHV based on its viral phylogeny as a highly mutable RNA virus. Overall, the importance of studying this disease lay not only in furthering our understanding of its transmission dynamics on the whole, but given that MHV is being used today as a blueprint for studying SARS-CoV-2 (COVID-19), it is of the utmost importance that we move beyond the lab and not only broaden our understanding of how MHV operates in the natural environments that humans and mice share, but also the factors that may alter its spread in those contexts.