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1. Emergence and interstate spread of highly pathogenic avian influenza A(H5N1) in dairy cattle in the United States

   https://doi.org/10.1126/science.adq0900  

   Nguyen, Thao-Quyen; Hutter, Carl R; Markin, Alexey; Thomas, Megan; Lantz, Kristina; Killian, Mary Lea; Janzen, Garrett M; Vijendran, Sriram; Wagle, Sanket; Inderski, Blake; et al (April 2025, Science)

   Highly pathogenic avian influenza (HPAI) viruses cross species barriers and have the potential to cause pandemics. In North America, HPAI A(H5N1) viruses related to the goose/Guangdong 2.3.4.4b hemagglutinin phylogenetic clade have infected wild birds, poultry, and mammals. Our genomic analysis and epidemiological investigation showed that a reassortment event in wild bird populations preceded a single wild bird–to-cattle transmission episode. The movement of asymptomatic or presymptomatic cattle has likely played a role in the spread of HPAI within the United States dairy herd. Some molecular markers that may lead to changes in transmission efficiency and phenotype were detected at low frequencies. Continued transmission of H5N1 HPAI within dairy cattle increases the risk for infection and subsequent spread of the virus to human populations. 

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2. Using an adaptive modeling framework to identify avian influenza spillover risk at the wild-domestic interface

   https://doi.org/10.1038/s41598-024-64912-w  

   Prosser, Diann J; Kent, Cody M; Sullivan, Jeffery D; Patyk, Kelly A; McCool, Mary-Jane; Torchetti, Mia Kim; Lantz, Kristina; Mullinax, Jennifer M (December 2024, Scientific Reports)

   Abstract The wild to domestic bird interface is an important nexus for emergence and transmission of highly pathogenic avian influenza (HPAI) viruses. Although the recent incursion of HPAI H5N1 Clade 2.3.4.4b into North America calls for emergency response and planning given the unprecedented scale, readily available data-driven models are lacking. Here, we provide high resolution spatial and temporal transmission risk models for the contiguous United States. Considering virus host ecology, we included weekly species-level wild waterfowl (Anatidae) abundance and endemic low pathogenic avian influenza virus prevalence metrics in combination with number of poultry farms per commodity type and relative biosecurity risks at two spatial scales: 3 km and county-level. Spillover risk varied across the annual cycle of waterfowl migration and some locations exhibited persistent risk throughout the year given higher poultry production. Validation using wild bird introduction events identified by phylogenetic analysis from 2022 to 2023 HPAI poultry outbreaks indicate strong model performance. The modular nature of our approach lends itself to building upon updated datasets under evolving conditions, testing hypothetical scenarios, or customizing results with proprietary data. This research demonstrates an adaptive approach for developing models to inform preparedness and response as novel outbreaks occur, viruses evolve, and additional data become available. 

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3. Rapid evolution of A(H5N1) influenza viruses after intercontinental spread to North America

   https://doi.org/10.1038/s41467-023-38415-7  

   Kandeil, Ahmed; Patton, Christopher; Jones, Jeremy C.; Jeevan, Trushar; Harrington, Walter N.; Trifkovic, Sanja; Seiler, Jon P.; Fabrizio, Thomas; Woodard, Karlie; Turner, Jasmine C.; et al (May 2023, Nature Communications)

   Abstract Highly pathogenic avian influenza A(H5N1) viruses of clade 2.3.4.4b underwent an explosive geographic expansion in 2021 among wild birds and domestic poultry across Asia, Europe, and Africa. By the end of 2021, 2.3.4.4b viruses were detected in North America, signifying further intercontinental spread. Here we show that the western movement of clade 2.3.4.4b was quickly followed by reassortment with viruses circulating in wild birds in North America, resulting in the acquisition of different combinations of ribonucleoprotein genes. These reassortant A(H5N1) viruses are genotypically and phenotypically diverse, with many causing severe disease with dramatic neurologic involvement in mammals. The proclivity of the current A(H5N1) 2.3.4.4b virus lineage to reassort and target the central nervous system warrants concerted planning to combat the spread and evolution of the virus within the continent and to mitigate the impact of a potential influenza pandemic that could originate from similar A(H5N1) reassortants. 

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4. Mathematical Modeling Finds Disparate Interferon Production Rates Drive Strain-Specific Immunodynamics during Deadly Influenza Infection

   https://doi.org/10.3390/v14050906  

   Ackerman, Emily E.; Weaver, Jordan J.; Shoemaker, Jason E. (May 2022, Viruses)

   The timing and magnitude of the immune response (i.e., the immunodynamics) associated with the early innate immune response to viral infection display distinct trends across influenza A virus subtypes in vivo. Evidence shows that the timing of the type-I interferon response and the overall magnitude of immune cell infiltration are both correlated with more severe outcomes. However, the mechanisms driving the distinct immunodynamics between infections of different virus strains (strain-specific immunodynamics) remain unclear. Here, computational modeling and strain-specific immunologic data are used to identify the immune interactions that differ in mice infected with low-pathogenic H1N1 or high-pathogenic H5N1 influenza viruses. Computational exploration of free parameters between strains suggests that the production rate of interferon is the major driver of strain-specific immune responses observed in vivo, and points towards the relationship between the viral load and lung epithelial interferon production as the main source of variance between infection outcomes. A greater understanding of the contributors to strain-specific immunodynamics can be utilized in future efforts aimed at treatment development to improve clinical outcomes of high-pathogenic viral strains. 

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5. Culicoides-Specific Fitness Increase of Vesicular Stomatitis Virus in Insect-to-Insect Infections

   https://doi.org/10.3390/insects15010034  

   Rozo-Lopez, Paula; Drolet, Barbara S (January 2024, Insects)

   Messenger, Louisa Alexandra (Ed.)

   Vesicular stomatitis virus (VSV) is an arthropod-borne virus affecting livestock. In the United States, sporadic outbreaks result in significant economic losses. During epizootics, Culicoides biting midges are biological vectors and key to the geographic expansion of outbreaks. Additionally, Culicoides may play a role in VSV overwintering because females and males are capable of highly efficient venereal transmission, despite their relatively low virus titers. We hypothesized that VSV propagated within a midge has increased fitness for subsequent midge infections. To evaluate the potential host-specific fitness increase, we propagated three viral isolates of VSV in porcine skin fibroblasts and Culicoides cell lines. We then evaluated the viral infection dynamics of the different cell-source groups in Culicoides sonorensis. Our results indicate that both mammalian- and insect-derived VSV replicate well in midges inoculated via intrathoracic injection, thereby bypassing the midgut barriers. However, when the virus was required to infect and escape the midgut barrier to disseminate after oral acquisition, the insect-derived viruses had significantly higher titers, infection, and dissemination rates than mammalian-derived viruses. Our research suggests that VSV replication in Culicoides cells increases viral fitness, facilitating midge-to-midge transmission and subsequent replication, and further highlights the significance of Culicoides midges in VSV maintenance and transmission dynamics. 

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