Publications by authors named "S A Whelan"

Vaccines that cross-protect across serovars of () would be a beneficial intervention against emerging and persistent isolates of concern for the turkey industry. The 2017-2019 foodborne outbreak of serovar Reading (. Reading) revealed the need for effective control of this serovar in turkey production.

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The Arenaviridae family of segmented RNA viruses contains nearly 70 species with several associated with fatal haemorrhagic fevers, including Lassa, Lujo and Junin viruses. Lymphocytic choriomeningitis arenavirus (LCMV) is associated with fatal neurologic disease in humans and additionally represents a tractable model for studying arenavirus biology. Within cultured cells, a high proportion of LCMV spread is between directly neighbouring cells, suggesting infectivity may pass through intercellular connections, bypassing the canonical extracellular route involving egress from the plasma membrane.

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The continued emergence of SARS-CoV-2 variants and the threat of future Sarbecovirus zoonoses have spurred the design of vaccines that can induce broad immunity against multiple coronaviruses. Here, we use computational methods to infer ancestral phylogenetic reconstructions of receptor binding domain (RBD) sequences across multiple Sarbecovirus clades and incorporate them into a multivalent adenoviral-vectored vaccine. Mice immunized with this pan-Sarbecovirus vaccine are protected in the upper and lower respiratory tracts against infection by historical and contemporary SARS-CoV-2 variants, SARS-CoV, and pre-emergent SHC014 and Pangolin/GD coronavirus strains.

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Article Synopsis
  • SARS-CoV-2 infects host cells by using its spike protein's receptor binding domain (RBD) to bind to the ACE2 receptor, which is crucial for the virus's entry into cells.
  • The ACE2 receptor consists of several domains, with the peptidase domain (PD) being essential for its function as a viral receptor; however, the receptor needs to be close to the cell membrane for effective infection.
  • Researchers found that engineered proteins targeting the RBD can influence whether cells are susceptible or resistant to the virus, indicating potential paths for antiviral therapies.
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Objective: Pharmacologic or genetic manipulation of O-GlcNAcylation, an intracellular, single sugar post-translational modification, are difficult to interpret due to the pleotropic nature of O-GlcNAc and the vast signaling pathways it regulates.

Method: To address the pleotropic nature of O-GlcNAc, we employed either OGT (O-GlcNAc transferase), OGA (O-GlcNAcase) liver knockouts, or pharmacological inhibition of OGA coupled with multi-Omics analysis and bioinformatics.

Results: We identified numerous genes, proteins, phospho-proteins, or metabolites that were either inversely or equivalently changed between conditions.

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