Biology subjects

Nelson, M. I.

Publications and source records attributed to Nelson, M. I..

15 recordsLinked to original sources

bioRxiv2026

Dairy cattle movement networks govern the spread and persistence of H5N1 B3.13 in the United States

Avian influenza virus H5N1 is predominantly found in wild and domestic birds. H5N1 genotype B3.13 was first detected in United States dairy cattle in March 2024 and spread through much of the country during 2024 and 2025, resulting in the largest known H5N1 outbreak in domestic mammals. By analysing viral genomic data jointly with historical cattle movement patterns, we find that live cattle movement is the predominant contributor to H5N1 spatial spread, rather than wild or domestic birds. Using phylogeographic methods we estimate that >40% of interstate viral transmissions occurred before B3.13's first detection and >70% occurred before interstate dairy cattle movement restrictions were implemented in April 2024. After this implementation, interstate transmission slowed but within-state spread persisted, driven by local cattle network density and movement volume. Our epidemic simulations demonstrate that the connectivity of counties within and around the Texas Panhandle - where the earliest cases were documented - predisposed the region to become an outbreak epicentre. Counterfactual simulations indicate that interstate restrictions needed to have begun 2-3 months earlier in order to limit the epizootic substantively, given the extent of cryptic spread before detection. Network-informed interventions outperformed geographically-defined containment, but response speed (rather than intervention strength) was the limiting factor in our epidemic models, underscoring the need for surveillance systems capable of detecting pathogen emergence before widespread dissemination.

evolutionary biology↗

bioRxiv2026

H5N5 virus transmission is driven by repeated cross-Atlantic introductions and transmission among high latitude seabirds

In November 2025, the first global H5N5 infection was reported in a person in Washington State. Previously, these viruses had only been detected in seabirds and shorebirds near the Atlantic Ocean, suggesting potentially distinct ecology from dominant H5N1 strains. Using 354 global H5N5 genomes, we show that H5N5 viruses have been carried by high latitude seabirds and shorebirds across the Atlantic at least 9 times, with introductions more frequent in the fall and spring. We reconstruct a plausible path of cross-continental movement via Arctic or sub-Arctic regions, followed by a year of cryptic circulation prior to human spillover. These data show that H5N5 viruses have undergone far more intercontinental movements than previously recognized, and exhibit host and geographic patterns that are fundamentally distinct from dominant H5N1 lineages. The distinct host ecology, geography, and movement, paired with the capacity to infect a person, suggest that enhanced surveillance may be warranted.

evolutionary biology↗

bioRxiv2026

Zoonotic infections and genomic evolution associated with novel reassortants swine-origin influenza A viruses in Spain

Influenza A virus (IAV) circulates widely in European pig populations and continues to diversify through frequent introductions from humans, followed by reassortment within swine. Spain represents a particularly dynamic ecological setting due to the coexistence of intensive whitepig production, extensive Iberianpig systems, and abundant wild boar populations. This study provides an integrated analysis of IAV evolution and genomic diversity in swine in Spain between 2019 and 2022, expanding on previous surveillance from 2016 to 2019. Sampling across 24 provinces yielded 66 new wholegenome sequences from Iberian and white pigs. We identified 18 genotypes, including 11 novel reassortants not detected in our previous survey. Several genotypes, such as H1huN2 G21 and G22, H3N2 G23, and the unusual H3N1 G12, were exclusive to the country. Some genotypes were detected across white pigs, Iberian pigs, and wild boar in Toledo and Badajoz, suggesting viral flow among swine populations. Phylogenetic analyses revealed ongoing introductions of H1N1pdm09 from humans into pigs, generating at least five reassortant genotypes (G10, G16-G19). These lineages incorporated pandemic internal cassettes and, in some cases, humanseasonal N2 segments, highlighting the continued role of humans as a source of viral incursions. Conversely, four zoonotic infections (H1N1v) detected in Spain between 2022 and 2026 were linked to genotypes circulating in white pigs, underscoring the bidirectional nature of IAV transmission at the human swine interface. Overall, this study demonstrates that Spain provides ecological conditions conducive to IAV diversification, reassortment, and zoonotic risk. The findings reinforce the need for sustained One Health surveillance. HighlightsO_LINovel swine influenza virus (SIV) genotypes exclusive to Spain C_LIO_LIPhylogenetic analysis of genomic segments of zoonotic variants of swine origin detected in Spain since 2022 C_LIO_LIShared circulation of influenza A compatible with interbreed transmission among domestic pigs and wild boar C_LI

evolutionary biology↗

bioRxiv2026

The emergence and molecular evolution of H5N1 influenza viruses in United States dairy cattle

Prior to 2024, highly pathogenic avian influenza H5N1 clade 2.3.4.4b viruses circulated predominantly in wild birds and poultry. In 2024 and 2025, 2.3.4.4b genotypes B3.13 and D1.1 were detected in United States dairy cattle. Using whole-genome and segment-specific phylodynamic inference, we estimate that B3.13 and D1.1 spilled over from wild birds into dairy cattle in late 2023 and late 2024, respectively. Spillover occurred shortly after the formation of the reassortant genotypes and was followed by months of cryptic transmission prior to detection. We found that both B3.13 and D1.1 evolved at higher rates in cattle relative to birds, primarily due to relaxed purifying selection. Site-specific analyses identified genomic sites under positive selection in cattle relative to birds, indicating adaptation and likely contributing to improved viral fitness after spillover. Intensified genomic surveillance in dairy cattle is essential as population immunity introduces additional selection pressures, with ever-changing risk for human emergence.

evolutionary biology↗

bioRxiv2025

Emergence of D1.1 reassortant H5N1 avian influenza viruses in North America

Since 2021, highly pathogenic avian influenza viruses (HPAIVs) belonging to H5N1 clade 2.3.4.4b have circulated widely in North American wild birds and repeatedly spilled over into mammals. In 2025, the first H5N1-associated deaths in humans were recorded in the Western hemisphere, raising questions about how the ongoing evolution of the virus in wild birds impacts spillover risk. Here, our analysis of 21,471 H5N1 genomes identified an evolutionary shift in mid-2024, driven by interhemispheric migration from Asia and reassortment with new antigens. The genotypes that dominated the early years of North Americas H5N1 epizootic traced their ancestry back to Europe, but Asia was the source of new "D1.1" genotype viruses that (a) spread faster, (b) have higher reassortment potential, (c) a broader host range, (d) repeatedly spill over to bovines, and (e) cause severe disease in humans, including non-farm workers.

evolutionary biology↗

bioRxiv2025

Novel Highly Pathogenic Avian Influenza (A)H5N1 Triple Reassortant in Argentina, 2025

Genomic sequencing of re-emerging highly pathogenic avian influenza A(H5N1) virus detected in Argentina in February 2025 revealed novel triple-reassortant viruses containing gene segments from Eurasian H5N1 and low pathogenic viruses from South and North American lineages. These findings underscore continued evolution and diversification of clade 2.3.4.4b H5N1 in the Americas.

genomics↗

bioRxiv2024

Massive outbreak of Influenza A H5N1 in elephant seals at Peninsula Valdes, Argentina: increased evidence for mammal-to-mammal transmission

H5N1 high pathogenicity avian influenza (HPAI) viruses of the clade 2.3.4.4b have killed thousands of marine mammals in South America since 2022. In October 2023, following outbreaks in sea lions in Argentina, we recorded unprecedented mass mortality ([~]17,000 individuals) in southern elephant seals (Mirounga leonina) at Peninsula Valdes. Seal pups were disproportionately affected. Adult seals departed early, disrupting social and breeding structure. Frequent interactions with sea lions and scavenging by seagulls were observed. Deaths of terns concurred with seals but peaked weeks later. HPAI H5N1 was confirmed in seals and terns. Moreover, genomic characterization showed viruses from pinnipeds and terns in Argentina form a distinct clade with marine mammal viruses from Peru, Chile and Brazil. These mammal-clade viruses share an identical set of mammalian adaptation mutations which are notably also found in the terns. Our combined ecological and phylogenetic data support mammal-to-mammal transmission and occasional mammal-to-bird spillover. To our knowledge, this is the first multinational transmission of H5N1 viruses in mammals ever observed globally. The implication that H5N1 viruses are becoming more evolutionary flexible and adapting to mammals in new ways could have global consequences for wildlife, humans, and/or livestock.

microbiology↗

bioRxiv2023

Highly pathogenic avian influenza A (H5N1) in marine mammals and seabirds in Peru

Highly pathogenic avian influenza (HPAI) A/H5N1 viruses (lineage 2.3.4.4b) are rapidly invading the Americas, threatening wildlife, poultry, and potentially evolving into the next global pandemic. In November 2022, HPAI arrived in Peru, where massive pelican and sea lion die-offs are still underway. We report complete genomic characterization of HPAI/H5N1 viruses in five species of marine mammals and seabirds (dolphins, sea lions, sanderlings, pelicans and cormorants) sampled since November 2022. All Peruvian viruses belong to the HPAI A/H5N1 lineage 2.3.4.4b, but they are 4:4 reassortants where 4 genomic segments (PA, HA, NA and MP) position within the Eurasian lineage that initially entered North America from Eurasia, while the other 4 genomic segments (PB2, PB1, NP and NS) position within the American lineage (clade C) that was already circulating in North America. These viruses are rapidly accruing mutations as they spread south. Peruvian viruses do not contain PB2 E627K or D701N mutations linked to mammalian host adaptation and enhanced transmission, but at least 8 novel polymorphic sites warrant further examination. This is the first report of HPAI A/H5N1 in marine birds and mammals from South America, highlighting an urgent need for active local surveillance to manage outbreaks and limit spillover into humans.

genomics↗

bioRxiv2022

Origins and Evolution of Seasonal Human Coronaviruses

Four seasonal human coronaviruses (sHCoVs) are endemic globally (229E, NL63, OC43, and HKU1), accounting for 5-30% of human respiratory infections. However, the epidemiology and evolution of these CoVs remain understudied due to their association with mild symptomatology. Using a multigene and complete genomes analysis approach, we find the evolutionary histories of sHCoVs to be more complex than previously recognized, owing to frequent recombination of CoVs, including within and between sHCoVs. Within sHCoV recombination rate was highest for 229E and OC43, and within genus highest for betaCoVs, whereas substitutions per recombination event inversely highest in NL63 and HKU1, and the alphaCoVs. Depending on the gene studied, OC43 may have ungulate, canine, or rabbit CoV ancestors, while 229E may have origins in a bat, camel or an unsampled intermediate host. HKU1 had the earliest most recent common ancestor (MRCA: 1809-1899), comprised two genetically divergent genotypes (A and B) possibly representing two independent transmission events from murine CoVs, and genotype B was genetically more diverse than all the other sHCoVs. Finally, we found shared amino acid substitutions in multiple proteins along the non-human to sHCoV host-jump branches. The complex evolution of CoVs and their frequent host switches could benefit from continued surveillance of CoVs across non-human hosts.

evolutionary biology↗

bioRxiv2022

Evolution of influenza A virus hemagglutinin H1 and H3 across host species

The Influenza A virus (IAV) hemagglutinin protein (HA) has been studied extensively, but its evolution has not been thoroughly compared among major host species. We compared H3 and H1 evolutionary rates among 49 lineages differentiated by host (avian, canine, equine, human, swine), phylogeny, and geography. Rates of nonsynonymous evolution, relative to synonymous rates, were higher in mammalian than avian hosts. Human seasonal HA and classical swine H1 accumulated 11-13 glycosylation sites, primarily in the antigenically important head domain, whereas lower numbers were maintained in other hosts. Canines had the highest ratio of nonsynonymous to synonymous changes in the more conserved stalk domain. Amino acid changes in canine viruses occurred disproportionately at residues located at protein interfaces. This suggests that they were adaptations affecting the major structural rearrangement of HA, which is critical for cell entry. These findings invite further study of how host ecology and physiology affect natural selection. AUTHOR SUMMARYInfluenza virus evolution is of practical importance to health in addition to being an excellent system for the study of parasite/host evolution. Our work explores a largely untapped aspect of influenza evolution: sequence evolution in non-human hosts. This is important in its own right, in terms of both science and domestic animal health. It also puts the evolution of human influenza in a larger, comparative context. Our results also provide evidence concerning the evolution of the hemagglutinin stem domain, which has not been a focus of study but has new importance due to the development of stem-based universal influenza vaccines.

evolutionary biology↗

bioRxiv2021

SARS-CoV-2 infection in free-ranging white-tailed deer (Odocoileus virginianus)

Human-to-animal spillover of SARS-CoV-2 virus has occurred in a wide range of animals, but thus far, the establishment of a new natural animal reservoir has not been detected. Here, we detected SARS-CoV-2 virus using rRT-PCR in 129 out of 360 (35.8%) free-ranging white-tailed deer (Odocoileus virginianus) from northeast Ohio (USA) sampled between January-March 2021. Deer in 6 locations were infected with at least 3 lineages of SARS-CoV-2 (B.1.2, B.1.596, B.1.582). The B.1.2 viruses, dominant in Ohio at the time, spilled over multiple times into deer populations in different locations. Deer-to-deer transmission may have occurred in three locations. The establishment of a natural reservoir of SARS-CoV-2 in white-tailed deer could facilitate divergent evolutionary trajectories and future spillback to humans, further complicating long-term COVID-19 control strategies. One-Sentence SummaryA significant proportion of SARS-CoV-2 infection in free-ranging US white-tailed deer reveals a potential new reservoir.

molecular biology↗

bioRxiv2020

Accommodating individual travel history, global mobility, and unsampled diversity in phylogeography: a SARS-CoV-2 case study.

Spatiotemporal bias in genome sequence sampling can severely confound phylogeographic inference based on discrete trait ancestral reconstruction. This has impeded our ability to accurately track the emergence and spread of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Despite the availability of unprecedented numbers of SARS-CoV-2 genomes on a global scale, evolutionary reconstructions are hindered by the slow accumulation of sequence divergence over its relatively short transmission history. When confronted with these issues, incorporating additional contextual data may critically inform phylodynamic reconstructions. Here, we present a new approach to integrate individual travel history data in Bayesian phylogeographic inference and apply it to the early spread of SARS-CoV-2, while also including global air transportation data. We demonstrate that including travel history data for each SARS-CoV-2 genome yields more realistic reconstructions of virus spread, particularly when travelers from undersampled locations are included to mitigate sampling bias. We further explore methods to ameliorate the impact of sampling bias by augmenting the phylogeographic analysis with lineages from undersampled locations in the analyses. Our reconstructions reinforce specific transmission hypotheses suggested by the inclusion of travel history data, but also suggest alternative routes of virus migration that are plausible within the epidemiological context but are not apparent with current sampling efforts. Although further research is needed to fully examine the performance of our travel-aware phylogeographic analyses with unsampled diversity and to further improve them, they represent multiple new avenues for directly addressing the colossal issue of sample bias in phylogeographic inference.

evolutionary biology↗

bioRxiv2020

The emergence of SARS-CoV-2 in Europe and the US

Accurate understanding of the global spread of emerging viruses is critically important for public health response and for anticipating and preventing future outbreaks. Here, we elucidate when, where and how the earliest sustained SARS-CoV-2 transmission networks became established in Europe and the United States (US). Our results refute prior findings erroneously linking cases in January 2020 with outbreaks that occurred weeks later. Instead, rapid interventions successfully prevented onward transmission of those early cases in Germany and Washington State. Other, later introductions of the virus from China to both Italy and Washington State founded the earliest sustained European and US transmission networks. Our analyses reveal an extended period of missed opportunity when intensive testing and contact tracing could have prevented SARS-CoV-2 from becoming established in the US and Europe.

genetics↗

bioRxiv2019

Phylogeographic and phylodynamic approaches to epidemiological hypothesis testing

Computational analyses of pathogen genomes are increasingly used to unravel the dispersal history and transmission dynamics of epidemics. Here, we show how to go beyond historical reconstructions and use spatially-explicit phylogeographic and phylodynamic approaches to formally test epidemiological hypotheses. We illustrate our approach by focusing on the West Nile virus (WNV) spread in North America that has been responsible for substantial impacts on public, veterinary, and wildlife health. WNV isolates have been sampled at various times and locations across North America since its introduction to New York twenty years ago. We exploit this genetic data repository to demonstrate that factors hypothesised to affect viral dispersal and demography can be formally tested. Specifically, we detail and apply an analytical workflow consisting of state-of-the art methods that we further improve to test the impact of environmental factors on the dispersal locations, velocity, and frequency of viral lineages, as well as on the genetic diversity of the viral population through time. We find that WNV lineages tend to disperse faster in areas with higher temperatures and we identify temporal variation in temperature as a main predictor of viral genetic diversity through time. Using a simulation procedure, we find no evidence that viral lineages preferentially circulate within the same migratory bird flyway, suggesting a substantial role for non-migratory birds or mosquito dispersal along the longitudinal gradient. Finally, we also separately apply our testing approaches on the three WNV genotypes that circulated in North America in order to understand and compare their dispersal ability. Our study demonstrates that the development and application of statistical approaches, coupled with comprehensive pathogen genomic data, can address epidemiological questions that might otherwise be difficult or impractically expensive to answer.

evolutionary biology↗

bioRxiv2017

Hemagglutinin Glycan Clock Guides Human Influenza A Virus Evolution

Adaptive immunity to influenza A virus is limited by frequent mutations in the immunodominant head of hemagglutinin (HA). Over the last century, the upward trend in HA-head glycosylation indicates glycan addition can increase fitness, but its role in viral evolution remains unclear. Here, we report glycan evolution follows a clock-like rhythm, pacing the timeline, trajectory, and replacement of HA. Following pandemic introduction, glycans are added to HA at 4- to 6-year intervals, until a functional glycan limit is reached, after which, at 9- to 12-year intervals, glycans are either swapped between different sites, or the HA is replaced by a novel pandemic virus. Using this, we predicted the appearance of the newest glycan on pH1N1 HA. Phylogeographic reconstruction suggests these highly fit strains originated in the Middle East, before rapidly replacing all strains globally. Going forward, we can use this simple algorithm to forecast future glycan evolution and identify seasons with higher pandemic potential.

microbiology↗