Biology subjects

Buckley, A. C.

Publications and source records attributed to Buckley, A. C..

3 recordsLinked to original sources

bioRxiv2025

Porcine epidemic diarrhea virus infection promotes Peyer's patch immune induction and epithelial defense via single-cell transcriptional reprogramming

Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus causing gastrointestinal disease in swine. To mitigate PEDV risks to swine health, agricultural economic losses, and global food security, a better understanding of host-pathogen interactions is required. Using single-cell RNA sequencing (scRNA-seq), we studied transcriptional cellular responses to PEDV infection in two anatomical compartments of intestinal jejunum: first-line barrier defenses of epithelia and underlying immune induction in Peyers patches. PEDV infection altered gene expression across all cell types and was associated with antiviral response pathways, indicating coordinated transcriptional reprogramming of diverse cell types. Signaling network inferences showed macrophages, dendritic cells, and non-resting B cells had increased signaling to T follicular helper cells associated with processes of T cell-dependent B cell activation during PEDV infection, indicating transcriptional promotion of immune induction in Peyers patches. Mature enterocytes were the primary targets for PEDV infection, and a 190-gene signature indicative of antiviral immune defense represented a conserved enterocyte response to PEDV infection, regardless of enterocyte stress state or infection status. The 190-gene signature was specific to the epithelial lineage and escalated with enterocyte maturation, indicating antiviral transcriptional reprogramming is mobilized across matured enterocytes of PEDV-infected intestinal segments. Results exemplify key roles of Peyers patches and epithelia as integral components for coordinated antiviral responsiveness in the intestine. Improved understandings of host-pathogen interactions during PEDV infection can identify indicators of PEDV protection versus susceptibility to target for future intervention strategies. IMPORTANCEPorcine epidemic diarrhea virus (PEDV) causes high death rates in young pigs and production losses in older animals, yet prevention and treatment options for PEDV remain limited. Understanding how PEDV infects pigs and how cells can control infection is crucial for developing better prevention and treatment strategies. Our work explores how intestinal cells are impacted by PEDV infection. We find all intestinal cells responded to infection despite diverse origins and functions. Processes promoting immune responses and epithelial barrier defenses against PEDV were initiated, culminating in a highly coordinated and conserved antiviral response. Results identify targets that may be useful in developing new PEDV prevention and control strategies that could positively impact animal health, agricultural economic prosperity, and global food security.

immunology↗

bioRxiv2025

United States PRRSV 1-4-4 L1C.5 isolate demonstrates similar pathogenicity to a historic Chinese highly pathogenic PRRSV

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major economic and animal health burden on the United States swine industry due to morbidity- and mortality-associated losses affecting all stages of pig production. Currently, a large proportion of losses are attributed to a highly virulent PRRSV strain, PRRSV 1-4-4 L1C.5. To benchmark the virulence of PRRSV 1-4-4 L1C.5, a study was conducted to compare pathogenicity of this contemporary strain to a historical Chinese highly pathogenic PRRSV (HP-PRRSV) strain, JXwn06, that devastated the Chinese and other Asian swine industries since 2006, as well as a moderately virulent United States PRRSV strain, MN184, considered to be one of the most virulent PRRSV strains circulating in the United States in the early 2000s. Weaned pigs were inoculated with PRRSV strains L1C.5, JXwn06, MN184, or mock inoculum and necropsied at 2, 6, and 10 days post inoculation, or as needed due to severe disease. Clinical metrics, viral loads, cytokine concentrations, PRRSV-specific antibody concentrations, and pathology were compared between treatment groups to compare pathogenicity. Results indicate a high degree of similarity disease dynamics between L1C.5 and JXwn06 animals that diverged from MN184 and mock animals. Findings indicate L1C.5 and JXwn06 cause more severe morbidity and mortality in weaned pigs than MN184. Results may be applied to develop more effective strategies for mitigating PRRSV 1-4-4 L1C.5 outbreaks currently plaguing the United States swine industry.

microbiology↗

bioRxiv2021

Susceptibility of white-tailed deer (Odocoileus virginianus) to SARS-CoV-2

The origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing the global coronavirus disease 19 (COVID-19) pandemic, remains a mystery. Current evidence suggests a likely spillover into humans from an animal reservoir. Understanding the host range and identifying animal species that are susceptible to SARS-CoV-2 infection may help to elucidate the origin of the virus and the mechanisms underlying cross-species transmission to humans. Here we demonstrated that white-tailed deer (Odocoileus virginianus), an animal species in which the angiotensin converting enzyme 2 (ACE2) - the SARS-CoV-2 receptor - shares a high degree of similarity to humans, are highly susceptible to infection. Intranasal inoculation of deer fawns with SARS-CoV-2 resulted in established subclinical viral infection and shedding of infectious virus in nasal secretions. Notably, infected animals transmitted the virus to non-inoculated contact deer. Viral RNA was detected in multiple tissues 21 days post-inoculation (pi). All inoculated and indirect contact animals seroconverted and developed neutralizing antibodies as early as day 7 pi. The work provides important insights into the animal host range of SARS-CoV-2 and identifies white-tailed deer as a susceptible wild animal species to the virus. IMPORTANCEGiven the presumed zoonotic origin of SARS-CoV-2, the human-animal-environment interface of COVID-19 pandemic is an area of great scientific and public- and animal-health interest. Identification of animal species that are susceptible to infection by SARS-CoV-2 may help to elucidate the potential origin of the virus, identify potential reservoirs or intermediate hosts, and define the mechanisms underlying cross-species transmission to humans. Additionally, it may also provide information and help to prevent potential reverse zoonosis that could lead to the establishment of a new wildlife hosts. Our data show that upon intranasal inoculation, white-tailed deer became subclinically infected and shed infectious SARS-CoV-2 in nasal secretions and feces. Importantly, indirect contact animals were infected and shed infectious virus, indicating efficient SARS-CoV-2 transmission from inoculated animals. These findings support the inclusion of wild cervid species in investigations conducted to assess potential reservoirs or sources of SARS-CoV-2 of infection.

microbiology↗