Biology subjects

Huey, D.

Publications and source records attributed to Huey, D..

5 recordsLinked to original sources

bioRxiv2026

Bovine-derived H5N1 influenza virus efficiently infects lactating swine via the mammary gland

Since 2024, highly pathogenic influenza A(H5N1) viruses have spread extensively among U.S. dairy cattle, where they replicate efficiently in the mammary gland and are shed at high titers in milk. To directly assess susceptibility of commercial swine populations to bovine-derived H5N1 virus, lactating sows with prior influenza virus vaccination histories representative of U.S. commercial swine production systems were inoculated via the intramammary route and co-housed with their 1-week-old piglets to evaluate disease outcomes, viral replication, and potential for vertical transmission. Intramammary inoculation of lactating sows resulted in sustained viral RNA shedding in milk, while piglets exhibited sporadic oral viral RNA positivity that mirrored viral kinetics in milk. Lesions in mammary tissue and viral antigen staining, as well as development of neutralizing antibody responses and changes in milk color and consistency, further confirmed infection in the sows. Despite these molecular findings, none of the animals developed overt clinical disease, and respiratory involvement was not noted during the study period. Collectively, we demonstrate that intramammary exposure results in productive influenza A(H5N1) virus infection in lactating sows despite their vaccination histories, indicating the potential threat of viral spillover into commercial swine populations. The clinically inapparent nature of infection presents a risk of subclinical spread and underscores the importance of expanding viral surveillance to swine.

microbiology↗

bioRxiv2026

A precision-cut lung slice platform for evaluating respiratory virus replication dynamics

Understanding respiratory virus replication, tropism, and disease mechanisms requires experimental systems that balance physiological relevance with scalability. Although immortalized cell lines remain widely used, they fail to capture the cellular complexity of the lung, while animal models--though informative--are often costly, low-throughput, and limited in their ability to model human disease. Here, we describe a rapid and scalable precision-cut lung slice (PCLS) platform that overcomes many of these limitations. Our workflow generates infection-ready lung tissue slices within 24 hours and maintains tissue viability over extended culture periods. Using influenza A virus as a model pathogen, we demonstrate that PCLS support robust viral replication, recapitulate characteristic infection-associated pathology, and elicit localized immune cell responses within the respiratory epithelium. Together, these features establish PCLS as a versatile and physiologically relevant platform for studying the biology of influenza virus and other respiratory pathogens.

microbiology↗

bioRxiv2026

Efficient replication of influenza D virus in the human airway underscores zoonotic potential

Influenza D virus (IDV), primarily found in livestock species, has demonstrated cross-species transmission potential, yet its threat to humans remains poorly understood. Here, we curated a panel of IDV isolates collected during field surveillance from 2011 to 2020 from swine and cattle to assess their ability to infect human airway cells as a proxy for zoonotic threat assessment. Using lung epithelial cell lines, primary well-differentiated airway epithelial cultures, and precision-cut lung slices, we demonstrated that IDV efficiently propagates in cells and tissues from the human respiratory tract, reaching titers comparable to human influenza A virus (IAV). Infection kinetics in primary porcine airway cultures and respiratory tissues mirrored those from human, suggesting similar infectivity across species. To define host responses to IDV infection, we evaluated innate immune sensing and downstream interferon signaling in human respiratory cells. IDV infection resulted in markedly reduced activation of interferon regulatory factor (IRF) signaling and diminished induction of interferon lambda 1 and interferon-stimulated genes compared to IAV, indicating inefficient activation of innate immune sensing pathways. However, IDV replication was potently restricted in interferon-pretreated cells, demonstrating sensitivity to interferon-mediated antiviral effector mechanisms once an antiviral state was established. Together, these findings show that IDV can efficiently infect the human airway while limiting innate immune sensing, a feature that may facilitate zoonotic spillover. Our study highlights the need for enhanced surveillance of IDV at the animal-human interface and provides a foundation for further investigation into its biology and potential for causing human infection and disease. SIGNIFICANCE STATEMENTInfluenza D virus (IDV) is a poorly understood virus type in the Orthomyxoviridae family. Although initially considered incapable of infecting humans, high seropositivity rates among cattle and swine workers suggest that zoonotic infections may already be occurring. However, the extent of human compatibility--and the potential for spillover--remains poorly understood. Our study demonstrates that IDV replicates efficiently in multiple human respiratory models while largely evading innate immune defenses, raising concern that only minimal evolutionary changes may be required for sustained human transmission. These findings underscore the need for further investigation into IDV biology and zoonotic risk. Such studies are critical for identifying viruses with the potential to adapt to humans before they become public health threats.

microbiology↗

bioRxiv2022

Surveillance for SARS-CoV-2 in Ohio's wildlife, companion, and agricultural animals

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in humans in late 2019 and spread rapidly to become a global pandemic. A zoonotic spillover event from animal to human was identified as the presumed origin. Subsequently, reports began emerging regarding spillback events resulting in SARS-CoV-2 infections in multiple animal species. These events highlighted critical links between animal and human health while also raising concerns about the development of new reservoir hosts and potential viral mutations that could alter virulence and transmission or evade immune responses. Characterizing susceptibility, prevalence, and transmission between animal species became a priority to help protect animal and human health. In this study, we coalesced a large team of investigators and community partners to surveil for SARS-CoV-2 in domestic and free-ranging animals around Ohio between May 2020 and August 2021. We focused on species with known or predicted susceptibility to SARS-CoV-2 infection, highly congregated or medically compromised animals (e.g. shelters, barns, veterinary hospitals), and animals that had frequent contact with humans (e.g. pets, agricultural animals, zoo animals, or animals in wildlife hospitals). This included free-ranging deer (n=76), mink (n=57), multiple species of bats (n=65), and other wildlife in addition to domestic cats (n=275) and pigs (n= 184). In total, we tested 800 animals (34 species) via rRT-PCR for SARS-CoV-2 RNA. SARS-CoV-2 viral RNA was not detected in any of the tested animals despite a major peak in human SARS-CoV-2 cases that occurred in Ohio subsequent to the peak of animal samplings. Importantly, due to lack of validated tests for animals, we did not test for SARS-CoV-2 antibodies in this study, which limited our ability to assess exposure. While the results of this study were negative, the surveillance effort was critical and remains key to understanding, predicting, and preventing re-emergence of SARS-CoV-2 in humans or animals.

microbiology↗

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↗