Host dependence of influenza A virus spatio-temporal dynamics

Emory University, Atlanta GA

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Abstract

SUMMARY Influenza A viruses (FLUAVs) circulate in a wide range of avian and mammalian hosts. Specific viral lineages are host restricted and tend to transmit among individuals of one or a small number of related species. Host range expansion is relatively common, however, with spillover between species occasionally giving rise to novel lineages and – with them – novel outbreaks. Owing to their implications for human and animal health, the drivers of and barriers to viral host range expansion garner significant attention. Much of this attention focuses at molecular and cellular levels, however, leaving a gap in understanding the impact of host differences on virus- host interactions that play out within tissues, between tissues and between individuals. These interactions are complex and multi-faceted. They are also highly consequential: they shape viral populations, define disease outcomes, and determine the potential for onward transmission. Thus, host specific differences in viral population structure and dynamics represent a major uncharted area of virology. To address this gap, we will examine FLUAV dynamics in a diverse set of host species, including multiple natural hosts, deploying state of the art viral genetics and next generation sequencing approaches to collect detailed spatial and temporal information as viral populations expand within hosts and transmit between them. Our overarching hypothesis is that viral populations are shaped predominantly by tissue tropism and transmission routes, such that parallels will be seen among disparate hosts in which FLUAV has a respiratory tropism, but categorically different viral dynamics will be apparent where FLUAV has enteric tropism or spreads systemically. To test this hypothesis, we will monitor barcoded virus libraries in ferrets, swine, mallards, chickens and quail. Systematic biopsy-based tissue sampling will be used to collect spatially resolved information while serial swab-based sampling will be used to collect longitudinal data. Results will enable a deep understanding of viral dissemination, a key driver of pathogenesis, and will define the extent to which stochastic processes shape viral evolutionary dynamics both within hosts and between hosts during transmission. Importantly, comparison of the patterns observed across species will reveal which of these aspects of FLUAV biology are common across hosts, and which are distinct, in turn furnishing novel insight into the virological and evolutionary consequences of host species transitions.