Host–Pathogen Interactions Influencing Zoonotic Spillover Potential and Transmission in Humans

Emerging infectious diseases of zoonotic origin are an ever-increasing public health risk and economic burden. The factors that determine if and when an animal virus is able to spill over into the human population with sufficient success to achieve ongoing transmission in humans are complex and dynamic. We are currently unable to fully predict which pathogens may appear in humans, where and with what impact. In this review, we highlight current knowledge of the key host–pathogen interactions known to influence zoonotic spillover potential and transmission in humans, with a particular focus on two important human viruses of zoonotic origin, the Nipah virus and the Ebola virus. Namely, key factors determining spillover potential include cellular and tissue tropism, as well as the virulence and pathogenic characteristics of the pathogen and the capacity of the pathogen to adapt and evolve within a novel host environment. We also detail our emerging understanding of the importance of steric hindrance of host cell factors by viral proteins using a “flytrap”-type mechanism of protein amyloidogenesis that could be crucial in developing future antiviral therapies against emerging pathogens. Finally, we discuss strategies to prepare for and to reduce the frequency of zoonotic spillover occurrences in order to minimize the risk of new outbreaks.