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High throughput characterization of bunyavirus diversity, ecology, and reassortment potential


Bunyavirales is an important group of viral pathogens with significant economic impacts. The Bunyavirales order contains the largest number of RNA viruses and can cause disease in plants, animals, and humans [1]. Notable plant pathogens include Tomato Spotted Wilt virus [2] which results in significant agricultural losses. Notable animal pathogens include Rift Valley fever virus [3] and Schmallenberg [4] virus resulting in significant livestock loss. Notable human pathogens include Crimean-Congo hemorrhagic fever virus [5], hantavirus [6], and La Crosse virus [7]. The effects of bunyavirus infections are felt worldwide because bunyaviruses are distributed globally. The emergence of novel bunyaviruses continues to threaten agricultural and livestock industries as well as human health. Where or when a novel bunyavirus might emerge is unknown. Predicting emergence is difficult for three reasons. First, because bunyaviruses are RNA viruses [8], the high error-rate of the RNA-dependent RNA polymerase results in a large genetic diversity within a population of viruses [9]. Secondly, many important bunyaviruses are arthropod-borne [10], resulting in an intricate lifecycle between an invertebrate and vertebrate host. This results in constantly changing genetic diversity due to different selective pressures from different host types [11]. It also results in an ever-expanding geographic range as vector range expands due to climate change and vertebrate host range changes due to urbanization, industrialization, and deforestation [12–16]. Third, bunyaviruses have segmented genomes which allows them to reassort and produce viral progeny with an altered vector-host range, pathogenesis, and virulence [1,17,18]. Therefore, this body of work aims to increase our ability to understand bunyavirus emergence and reassortment potential as a way to aid in outbreak preparedness and early response systems. To do this, we've combined traditional surveillance data with modern bioinformatics to expand our knowledge of bunyavirus genetic diversity, ecology, and reassortment potential. Using whole-genome sequencing, we've characterized the genomes of 99 bunyaviruses, some of which have never been sequenced before. This aids in our understanding of the genetic diversity, co-infection dynamics, and reassortment potential. Next, we used existing metadata from orthobunyavirus sequences to determine reassortment potential given a shared geographic and vector-host range. Finally, we've developed a novel molecular assay to evaluate reassortment potential based on replication and transcription compatibility. Together, we've combined the strengths of viral surveillance and modern bioinformatics to demonstrate the benefit of combining both. We've developed systems that will help to delineate the mechanisms that either promote or inhibit reassortment potential, ultimately aiding in early response systems for outbreak preparedness.


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Embargo expires: 08/28/2025.



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