Martha Nelson Lab

  • Outbreak of H9N2 avian influenza viruses in lesser rhea in Peru, June-July 2025

    Avian influenza viruses (AIVs) are endemic in the Americas and responsible for outbreaks in both domestic and wild birds that occasionally spill over into humans. We report the first known outbreak of AIV H9N2 in lesser rhea (Rhea pennata), also known as Darwin’s rhea, in the region of Puno-Peru. The animals in this study lived in an isolated conservation center located in remote highlands above 4,000 m.a.s.l. Between June and July 2025, a total of 46/92 animals were recorded sick, with symptoms including greenish diarrhea (100%), hyporexia (24%), dyspnea (76%), nasal discharge (42%), drowsiness (18%) and isolation from the flock (73%), and 94% later died. Gross pathology exams revealed septicemia characterized by severe hepatitis, pneumonia, tracheitis, enteritis, and encephalitis. Swab and necropsy samples tested positive for Influenza A by PCR and were later identified as H9N2 through whole genome sequencing. We generated complete H9N2 genomes for two individuals. No additional pathogens were found. Phylogenetic analysis across all eight segments revealed that the viruses were low pathogenicity H9N2 AIV strains of North American origin, which indicated this outbreak was a new introduction of the virus into South America. We also performed a comparative mutational analysis and identified multiple mutations previously associated with mammalian host adaptation, increased virulence, increased pathogenicity, and increased virus binding to α2-6 receptors, which may explain the high mortality rates observed despite the supposedly low pathogenicity of the strain. We also identified novel mutations specific to rhea viruses that will need to be experimentally validated. This is the first report of a natural H9N2 systemic infection in an avian host, highlighting a need for increased surveillance efforts for zoonotic influenza viruses with pandemic potential.

  • SARS-CoV-2 Delta variant re-emerges in US farmed mink and free-ranging white-tailed deer in 2022-2023

    American mink (Neogale vison) are susceptible to SARS-CoV-2, but little is known about virus circulation in mink since 2021. Here, in the first active surveillance study of SARS-CoV-2 in apparently healthy farmed mink in the United States, we find a ~0.9% (760/85,656) RT-PCR positivity rate among nasal swabs collected in 18 farms across six states during 2022-2023. Phylogenetic analysis of 293 viral genome sequences shows that human-adapted SARS-CoV-2 variants (e.g., Omicron) repeatedly spill over into mink. Surprisingly, the detection of a Delta lineage virus (AY.39) on a mink farm four months after its last detection in humans within the same state suggests prolonged unsampled transmission. The spread of mink-adapted AY.39 viruses from a mink farm to neighboring free-ranging white-tailed deer represents a rare instance of SARS-CoV-2 transmission between livestock and wildlife. These findings demonstrate the value of active surveillance for identifying subclinical infections and interspecies transmission between humans, mink, and wildlife.

  • Highly pathogenic avian influenza (HPAI H5N1, clade 2.3.4.4b, genotype C2.1) in commercial ring-necked pheasants during the 2022 outbreak in the United States

    Highly pathogenic avian influenza (HPAI) virus H5N1 clade 2.3.4.4b was introduced into North America in 2021. In 2022, clade 2.3.4.4b spilled into domestic poultry in the United States (U.S.), resulting in the largest HPAI outbreak in U.S. history. In December 2023, H5N1 2.3.4.4b was detected on an upland game bird farm in Pennsylvania. History, clinical signs, and gross lesions were suggestive of marble spleen disease. However, HPAI was identified by real-time reverse-transcriptase polymerase chain reaction; gene sequencing confirmed genotype C2.1 with phylodynamic analyses providing evidence of a wild bird introduction. Predictive mathematical modeling estimated the time of virus introduction onto the farm (15 days (95% C.I., 11-23) before the date of confirmed detection) being similar or longer than previously described for domestic poultry. Although bioexclusion measures were unable to prevent the initial exposure due to industry rearing practices, biocontainment procedures appeared to prevent spread. The lessons learned from this case may be important for other animal agriculture commodities, especially those species that are infrequently handled or observed and may have inaccurately calculated mortality levels. This well-characterized outbreak and other experiences with natural infection should be taken as opportunities to better understand the field dynamics of this virus.

  • Can H5N1 avian influenza in dairy cattle be contained in the US?

    The emergence and sustained spread of H5N1 in US dairy cattle since 2024 have demonstrated that highly pathogenic avian influenza (HPAI) is capable of establishing long-term transmission in livestock. Genomic surveillance has clarified national patterns of spatial diffusion, interspecies transmission, and viral evolution, but critical data gaps remain that impede efforts to track virus movements in real time, identify modes of transmission, and inform control efforts.

  • CEIRR Risk Assessment Pipeline executive reports on H5N1 highly pathogenic avian influenza 2.3.4.4b, swine H1 1B.2, and H9N2 low pathogenicity avian influenza B4.7.2

    The Centers of Excellence for Influenza Research and Response (CEIRR) Risk Assessment Pipeline (RAP) integrates surveillance, phenotypic analysis, and computational modeling across six CEIRR centers to evaluate the pandemic potential of influenza A viruses. By generating coordinated data sets from wild and domestic animals and linking them to viral evolution and functional traits, CEIRR RAP supports the Centers for Disease Control and Prevention’s and the World Health Organization’s risk-assessment efforts. The RAP’s data packages thereby enable evidence-based prioritization of global influenza preparedness and response strategies.

  • 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.

  • 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 America’s 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.

  • The global H5N1 influenza panzootic in mammals

    Influenza A viruses have caused more documented global pandemics in human history than any other pathogen1,2. High pathogenicity avian influenza viruses belonging to the H5N1 subtype are a leading pandemic risk. Two decades after H5N1 ‘bird flu’ became established in poultry in Southeast Asia, its descendants have resurged3, setting off a H5N1 panzootic in wild birds that is fuelled by: (1) rapid intercontinental spread, reaching South America and Antarctica for the first time4,5; (2) fast evolution via genomic reassortment6; and (3) frequent spillover into terrestrial7,8 and marine mammals9. The virus has sustained mammal-to-mammal transmission in multiple settings, including European fur farms10,11, South American marine mammals12-15 and US dairy cattle16-19, raising questions about whether humans are next. Historically, swine are considered optimal intermediary hosts that help avian influenza viruses adapt to mammals before jumping to humans20. However, the altered ecology of H5N1 has opened the door to new evolutionary pathways. Dairy cattle, farmed mink or South American sea lions may have the potential to serve as new mammalian gateways for transmission of avian influenza viruses to humans. In this Perspective, we explore the molecular and ecological factors driving the sudden expansion in H5N1 host range and assess the likelihood of different zoonotic pathways leading to an H5N1 pandemic.

  • Persistence of SARS-CoV-2 Alpha Variant in White-Tailed Deer, Ohio, USA

    Free-ranging white-tailed deer (WTD) are highly susceptible to the SARS-CoV-2 virus. Through an opportunistic sampling of WTD in northeast Ohio, USA, during January-March 2023, we identified 6 SARS-CoV-2 lineages from 36 sequences using the pangolin lineages tool, including the B.1.1.7 lineage (Alpha variant) and BQ.1.1, BQ.1.1.63, BQ.1.1.67, BQ.1.23, and XBB.1.5.35 lineages (Omicron variant). The Alpha variant, introduced by a single human-to-deer transmission event, was detected in 5 WTD in January 2023, more than 1 year after the most recent detection of the Alpha variant in humans in Ohio (August 2021). A genetically similar B.1.1.7 lineage virus from WTD in a nearby county in Pennsylvania was positioned with our Ohio deer transmission cluster, suggesting deer-to-deer transmission. The persistence of the Alpha variant in WTD in Ohio warrants continued surveillance to monitor if WTD can become a reservoir for displaced SARS-CoV-2 variants.

  • Controlling bird flu is urgent-for dairy, wildlife, poultry, pets, and people

    Highly pathogenic avian influenza viruses of the H5N1 subtype have recently undergone a major geographic expansion. At the same time, these viruses have substantially broadened their host range. Typically, H5N1 circulates in poultry, waterfowl, and shorebirds, but the breadth of avian species affected has increased and spillover to mammals has become common. The recent changes in H5N1 ecology have brought die-offs in wild birds and marine mammals, a sustained outbreak in US dairy cattle, and recurring spillover into domestic cats. Maintenance of H5N1 in wild birds in North America has furthermore produced a persistent risk to US poultry. Circulation of H5N1 in domestic animals has resulted in human infections, especially among farm workers and veterinarians, events that heighten the potential for a pandemic. Through their central position in One Health, veterinarians have a critical role to play in mitigating the impact of H5N1 on animal health, agriculture, and public health.