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Administration of antigenically distinct influenza viral particle combinations as an influenza vaccine strategy.
PLoS Pathog
January 2025
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, United States of America.
One approach for developing a more universal influenza vaccine is to elicit strong immune responses against canonically immunosubdominant epitopes in the surface exposed viral glycoproteins. While standard vaccines typically induce responses directed primarily against mutable epitopes in the hemagglutinin (HA) head domain, there are generally limited or variable responses directed against epitopes in the relatively more conserved HA stalk domain and neuraminidase (NA) proteins. Here we describe a vaccine approach that utilizes a combination of wildtype (WT) influenza virus particles along with virus particles engineered to display a trimerized HA stalk in place of the full-length HA protein to elicit both responses simultaneously.
View Article and Find Full Text PDFThe peculiar characteristics and advancement in diagnostic methodologies of influenza A virus.
Front Microbiol
January 2025
CAS Key Laboratory of Molecular Virology and Immunology, Institutional Center for Shared Technologies and Facilities, Pathogen Discovery and Big Data Platform, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, China.
Influenza A virus (IAV) is a significant public health concern, causing seasonal outbreaks and occasional pandemics. These outbreaks result from changes in the virus's surface proteins which include hemagglutinin and neuraminidase. Influenza A virus has a vast reservoir, including wild birds, pigs, horses, domestic and marine animals.
View Article and Find Full Text PDFNeuraminidase 1 regulates neuropathogenesis by governing the cellular state of microglia via modulation of Trem2 sialylation.
Cell Rep
January 2025
Department of Genetics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Anatomy and Neurobiology, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address:
Neuraminidase 1 (NEU1) cleaves terminal sialic acids from sialoglycoproteins in endolysosomes and at the plasma membrane. As such, NEU1 regulates immune cells, primarily those of the monocytic lineage. Here, we examine how Neu1 influences microglia by modulating the sialylation of full-length Trem2 (Trem2-FL), a multifunctional receptor that regulates microglial survival, phagocytosis, and cytokine production.
View Article and Find Full Text PDFA Simple and Efficient Stereoselective Synthesis of a 2,3-Difluorosialic acid-based influenza virus neuraminidase inhibitor.
Chemistry
January 2025
Griffith University - Gold Coast Campus, Institute for Biomedicine and Glycomics, Parklands Drive, 4222, Southport, AUSTRALIA.
3-Fluoroneuraminosyl fluorides are invaluable probes for studying the catalytic mechanism of sialidases (neuraminidases), and as sialidase inhibitors. Significantly, when a C-3 equatorial fluorine is installed on a C-4 functionalised N-acylneuraminic acid (Neu)-based template, the compounds are potent and selective inhibitors of both influenza and parainfluenza sialidases, and of virus replication. Typically, the reported syntheses of 3-fluoroneuraminosyl fluorides involve either an enzymatic or a chemical synthesis that have uncontrolled stereoselectivity in the introduction of fluorine at C-3 of Neu and consequently yield a mixture of C-3 ax and C-3 eq fluoro derivatives.
View Article and Find Full Text PDFTranscriptome analysis reveals molecular targets of erythrocyte invasion phenotype diversity in natural isolates from Cameroon.
Front Parasitol
May 2024
Disease Control and Elimination (DCE), Medical Research Council The Gambia Unit at the London School of Hygiene and Tropical Medicine (LSHTM), Fajara, Gambia.
Further understanding of the molecular mediators of alternative RBC invasion phenotypes in endemic malaria parasites will support malaria blood-stage vaccine or drug development. This study investigated the prevalence of sialic acid (SA)-dependent and SA-independent RBC invasion pathways in endemic parasites from Cameroon and compared the schizont stage transcriptomes in these two groups to uncover the wider repertoire of transcriptional variation associated with the use of alternative RBC invasion pathway phenotypes. A two-color flow cytometry-based invasion-inhibition assay against RBCs treated with neuraminidase, trypsin, and chymotrypsin and deep RNA sequencing of schizont stages harvested in the first replication cycle in culture were employed in this investigation.
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