YY-EEID US-UK The evolutionary ecology of pathogen emergence via cross-species transmission in the avian-equine influenza system

Viral emergence poses a constant threat to humans and animals and we are neither able to predict which viruses will emerge, nor where, when, or which populations will be affected. The overall aim of this project is to determine how environmental, host, and virus factors influence host-pathogen interactions and transmission dynamics of potentially emerging viruses. Avian influenza viruses (AIVs) provide unique opportunities to address this because they have jumped into humans, dogs, pigs and horses, with significant consequences on public health, food security, and the global economy. We will focus on the transmission and emergence of AIVs to horses because AIV strains have emerged in horse populations on independent occasions. We propose to perform field work in a well-defined ecosystem that favours avian-to-horse AIV transmission and also to perform laboratory experiments using avian and equine influenza viruses with different levels of "equine fitness" - ability to infect and transmit in horses. Our laboratory experiments will use genetic engineering to capture changes in fitness due to virus evolution. Results obtained will be combined in a mathematical framework that will enable the estimation of risk of viral emergence, including the effects of herd immunity. This multidisciplinary research will provide new insights on the mechanisms that underpin viral emergence and will aid the design of more effective intervention measures to control future events of viral emergence.

Generalist pathogens are the norm rather than the exception, with many pathogens, including viruses, capable of infecting host species that are distantly related to each other. For any particular pathogen, our mechanistic understanding of this host range is poor, yet this knowledge can potentially illuminate many host-pathogen association patterns in nature. Moreover, with the majority of emerging infectious diseases caused by zoonoses, identifying the barriers and bridges to cross-species transmission will support public health research and application.
Equine influenza viruses have been postulated as potential pandemic viruses because some virus strains derived from horses can infect humans, at least experimentally. Furthermore, from the 17th to the early 20th century, it has been noted that equine influenza epizootics coincided with major human outbreaks and epidemics. Although the world has replaced the horse as the major mode of transportation and, consequently, decreased the chances of human exposure to horse pathogens, this is not the case in Mongolia. Still to this day, horses play a major role in the lives of Mongols as a major mode of transport and an important source of milk and meat. Mongolia's horse population is ~3 million, similar to its human population size. Thus, Mongolia still is the one place in the world where the emergence of a novel pandemic influenza strain of equine origin is possible. This project will study the fundamental steps leading to novel pathogen emergence in a host species and a well-defined ecosystem through a linked set of research questions to obtain information on 1) dynamics of exposure to pathogens from donor to recipient species, 2) variation in fitness components of emerging and non-emerging pathogens in recipient species, 3) effects of small (mutation) and large (reassortment) genetic changes to pathogen fitness in recipient species, 4) consequences of immunity generated by previous exposures on pathogen emergence.