Zoological transmission of encephalomyocarditis virus in the United States: Virus evolution, host ecology, and capsid antigenicity derived from an outbreak

Abstract

Encephalomyocarditis virus (EMCV) is a rodent-borne picornavirus that has repeatedly caused severe outbreaks resulting in the deaths of zoo mammals – most notably elephants – for decades. However, within North America, little is known regarding the diversity of EMCV that exists in nature, the reservoir or amplifying hosts important for maintaining the virus, and the epidemiology of zoo-associated outbreaks. This lack of knowledge of the EMCV strains that circulate in North America has impeded a more thorough understanding of how genetic and antigenic variation may affect pathogenicity or potentially vaccine-induced protection from disease. Herein, following a zoological outbreak of EMCV in Florida, we conducted the most comprehensive comparative phylogenomic analysis of virus isolates from fatal zoo animal cases and local rodent species to date, identifying both non-native, invasive rodents and native mice and rat species as potentially important in precipitating and/or maintaining outbreaks, with multiple transmissions to zoo animals. After development of an autogenous vaccine, we investigated the duration and magnitude of neutralizing antibody responses in elephants monthly for multiple years, providing a unique fine-scale, long-term profile of responses to vaccination. To better understand how antigenic variation may affect vaccine-induced protection, we constructed a reverse genetics system to determine the level of cross-protection afforded by autogenous vaccination against capsids derived from various divergent EMCV strains and serotypes. These results provide new advancements in understanding EMCV transmission and antigenicity in North America, which can be used as a foundation to ultimately enable zoos to better protect animals from this important pathogen.