Publications by authors named "Sean Whelan"
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.
View Article and Find Full Text PDFThe 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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- 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.
Article Synopsis
- - SARS-CoV-2 has evolved to evade current monoclonal antibodies (mAbs), emphasizing the need for more resilient treatments that can neutralize various viral strains.
- - A new human mAb called VIR-7229 has shown the ability to effectively neutralize multiple variants of SARS-CoV-2 and other related viruses, due to its unique targeting of a critical viral region known as the receptor-binding motif (RBM).
- - VIR-7229 demonstrates a high resistance to the emergence of virus escape mutants, making it a promising candidate for future therapies against evolving coronaviruses.
Article Synopsis
- VLDLR has been identified as a receptor for several alphaviruses, including Western equine encephalitis virus (WEEV), and may play a role in their infection process.
- Research shows that mice lacking VLDLR have reduced susceptibility to WEEV, EEEV, and Semliki Forest virus (SFV), indicating its importance in alphavirus pathogenesis.
- The findings suggest that targeting VLDLR could be a potential strategy for developing treatments against various alphavirus infections.
Article Synopsis
- Most pandemic viruses have a protective covering and enter cells through a specific method that involves helper proteins.
- Researchers found that a protein called TRPM7 is very important for these viruses to infect cells, as it helps create the right conditions inside the cell for the virus to fuse and enter.
- The study suggests that targeting TRPM7 could lead to new medicines that could prevent many types of these viruses from infecting cells.
Science is humanity's best insurance against threats from nature, but it is a fragile enterprise that must be nourished and protected. The preponderance of scientific evidence indicates a natural origin for SARS-CoV-2. Yet, the theory that SARS-CoV-2 was engineered in and escaped from a lab dominates media attention, even in the absence of strong evidence.
View Article and Find Full Text PDFLymphocytic choriomeningitis virus (LCMV) is an enveloped and segmented negative-sense RNA virus classified within the family of the order. LCMV is associated with fatal disease in immunocompromised populations and, as the prototypical arenavirus member, acts as a model for the many highly pathogenic members of the family, such as Junín, Lassa, and Lujo viruses, all of which are associated with devastating hemorrhagic fevers. To enter cells, the LCMV envelope fuses with late endosomal membranes, for which two established requirements are low pH and interaction between the LCMV glycoprotein (GP) spike and secondary receptor CD164.
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- Researchers studied how mRNA vaccine boosters affect antibody responses in both mice and humans, finding that initial vaccine doses influenced responses to newer variants.
- In humans, receiving Omicron-matched boosters after prior vaccinations led to a broadened antibody response, suggesting that imprinting can promote the production of antibodies that are effective against various SARS-CoV-2 variants and related viruses.
The major determinant of blood culture (BC) diagnostic performance is blood volume, and pediatric sample volumes are frequently low. We aimed to assess BC volumes in our institution, design an intervention to increase volumes, and assess its impact. All pediatric BCs submitted over a 7-month period to the microbiology laboratory in a university hospital (including emergency department, pediatric ward, and neonatal unit) were included.
View Article and Find Full Text PDFBackground: Escherichia coli is the predominant urinary pathogen in children. Irish and international studies have demonstrated increasing antimicrobial resistance (AMR) to antibiotics such as co-amoxiclav.
Aims: We aimed to (1) examine the AMR patterns of paediatric urinary E.
There is limited information on the antibody responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in subjects from developing countries with populations having a high incidence of co-morbidities. Here, we analysed the immunogenicity of homologous schemes using the ChAdOx1-S, Sputnik V, or BNT162b2 vaccines and the effect of a booster dose with ChAdOx1-S in middle-aged adults who were seropositive or seronegative to the SARS-CoV-2 spike protein before vaccination. The study was conducted post-vaccination with a follow-up of 4 months for antibody titre using enzyme-linked immunosorbent assay (ELISA) and pseudovirus (PV) neutralization assays (PNAs).
View Article and Find Full Text PDFMost neutralizing anti-SARS-CoV-2 monoclonal antibodies (mAbs) target the receptor binding domain (RBD) of the spike (S) protein. Here, we characterize a panel of mAbs targeting the N-terminal domain (NTD) or other non-RBD epitopes of S. A subset of NTD mAbs inhibits SARS-CoV-2 entry at a post-attachment step and avidly binds the surface of infected cells.
View Article and Find Full Text PDFComplete genome sequence of phi29-like podovirus phage PineapplePizza.
Microbiol Resour Announc
October 2023
Bacteriophage PineapplePizza is a podovirus infecting NRRL B-24224. The genome is 16,662 bp long and contains 23 predicted protein-coding genes. Interestingly, PineapplePizza shows amino acid similarities to well-studied phage phi29.
View Article and Find Full Text PDFThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood.
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- Serine proteases, like factor Xa (FXa), play a crucial role in cleaving the SARS-CoV-2 spike protein, which is necessary for the virus's entry into cells.
- FXa is unique among serine proteases as it has antiviral properties that block the virus from binding to the ACE2 receptor, though it is less effective against certain variants.
- The study suggests that while FXa can prolong survival in models of COVID-19, the use of direct FXa inhibitors like rivaroxaban may hinder its protective effects, highlighting the need for caution when treating clotting issues in COVID-19 patients.
The primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses and the development of vaccines aimed at the new variants. SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells. However, it remains unclear whether the additional doses induce germinal centre reactions whereby re-engaged B cells can further mature, and whether variant-derived vaccines can elicit responses to variant-specific epitopes.
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- Viruses pose significant health challenges, leading to issues like respiratory infections, cancer, and neurological impairments, but virology research has developed vaccines and antivirals to mitigate these problems.
- The COVID-19 pandemic has heightened public scrutiny of virology, especially regarding the safe conduct of research with human pathogens, leading to confusion and misinterpretation about the origins of SARS-CoV-2.
- This article aims to clarify misconceptions by explaining gain-of-function research, the origins of SARS-CoV-2, and the regulatory frameworks in place, fostering informed discussions and emphasizing the need for balanced, evidence-based dialogue in virology.
Article Synopsis
- Viruses have historically caused serious health issues, including respiratory infections and cancer, leading to significant virology research that resulted in vaccines and antiviral treatments.
- The COVID-19 pandemic highlighted the necessity for careful research on human pathogens, creating both concerns and confusion about the safety of virology work and the origins of SARS-CoV-2.
- The article aims to clarify misunderstandings by explaining gain-of-function research, exploring the origins of SARS-CoV-2, and discussing regulatory oversight, while advocating for rational and evidence-based discussions to guide policy decisions in virology.
Article Synopsis
- Viruses pose significant health challenges, leading to various issues such as respiratory infections and cancer, prompting virology research to develop vaccines and antiviral treatments over the past 60+ years.
- The COVID-19 pandemic has intensified focus on virology, bringing up safety concerns about research involving human pathogens and creating public confusion between safe research practices and the origins of SARS-CoV-2.
- The article aims to clarify these issues by discussing gain-of-function research, the origins of SARS-CoV-2, and current regulatory frameworks, advocating for informed, balanced conversations to support necessary virology research.
Objective: Lateral flow assays (LFA) are sensitive for detecting antibodies to SARS-CoV-2 proteins within weeks after infection. This study tested samples from immunocompetent adults, and those receiving treatments for chronic inflammatory diseases (CID), before and after mRNA SARS-CoV-2 vaccination.
Methods: We compared results obtained with the COVIBLOCK Covid-19 LFA to those obtained by anti-spike (S) ELISA.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters elicit plasma-neutralizing antibodies against Omicron BA.1, BA.
View Article and Find Full Text PDFGenome Sequences of Microbacterium foliorum Phages Anseraureola, Pondwater, and Yasuo.
Microbiol Resour Announc
November 2022
Anseraureola, Pondwater, and Yasuo are bacteriophages with siphovirus morphology that infect Microbacterium foliorum NRRL B-24224. They were isolated from soil collected in Amherst, Massachusetts, and have genome lengths between 17,362 bp and 17,453 bp. These phages each contain 25 predicted protein-coding genes and are assigned to phage cluster EE.
View Article and Find Full Text PDFThe primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses of these vaccines and the development of new variant-derived ones . SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells (MBCs) . It remains unclear, however, whether the additional doses induce germinal centre (GC) reactions where reengaged B cells can further mature and whether variant-derived vaccines can elicit responses to novel epitopes specific to such variants.
View Article and Find Full Text PDFSARS-CoV-2 requires acidic pH to infect cells.
Proc Natl Acad Sci U S A
September 2022
Article Synopsis
- * Research using advanced tracking techniques reveals that an acidic environment (pH 6.2 to 6.8) is essential for the virus to effectively penetrate and release its genetic material into host cells, even after the initial cleavage events.
- * The study highlights the importance of acidic conditions, which are found in places like the nasal cavity, for enhancing SARS-CoV-2 infection, particularly in cells that express TMPRSS2.