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

Abstract

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.

Immune correlates of protection for SARS-CoV-2, Ebola and Nipah virus infection

“…NiV outbreaks are reported almost yearly, the most recent occurring in India in 2021, notably with one of the highest fatality rates (92%) observed in the last few years ( 149 ). NiV infection in humans is generally associated with an acute respiratory and neurological syndrome resulting in a high fatality rate of between 40% and 92%, depending on the local capacity for epidemiological surveillance and clinical management ( 150 – 152 ).…”

Redox-dependent formation of a viral amyloid and functional impact

“…They are zoonotic viruses responsible for severe encephalitis and respiratory illness with a high case fatality, and as such, they are considered high-priority targets by the WHO. Since the identification of HeV and NiV in humans and fruit-bats from the Pteropus genus (1, 2), new species have been described including the Cedar virus identified in bats (3), the Langya virus identified in patients, bats and shrews (4, 5) and two novel species in shrews (6). Transmission from bats to humans occurs through the consumption of raw date palm sap (NiV) or from close contact with infected livestock, particularly horses (HeV) and pigs (NiV) (7).…”

“…Beyond the P protein, the P gene also drives the synthesis of the V, W, and C proteins. The V and W proteins are produced through a co-transcriptional editing mechanism involving the addition of one (V) or two (W) non-templated G nucleotides at the editing site of the P messenger (2). In NiV-infected cells, equimolar proportions of P, V, and W transcripts are detected in the early stage of infection while the quantity of V and W transcripts increases as the infection progresses (10).…”

Cellular receptors for mammalian viruses

“…Mammals can be infected by thousands of viruses belonging to tens of different families. Cellular receptors and other entry factors critically determine infectivity and play a major role in viral cross-species transmission [1][2][3][4]. There are numerous examples showing the evolution of key mutations in viral receptor-binding proteins that promote transmissibility.…”