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Nano-Biomechanical Investigation of Phosphatidylserine-Mediated Ebola Viral Attachment via Human Gas6 and Axl.
Viruses
October 2024
Department of Bioengineering, Lehigh University, Bethlehem, PA 18015, USA.
The Ebola virus is a deadly pathogen that has been threatening public health for decades. Recent studies have revealed alternative viral invasion routes where Ebola virus approaches cells via interactions among phosphatidylserine (PS), PS binding ligands such as Gas6, and TAM family receptors such as Axl. In this study, we investigate the interactions among phosphatidylserine on the Ebola viral-like particle (VLP) membrane, human Gas6, and human Axl using atomic force microscope-based single molecule force spectroscopy to compare their binding strength and affinity from a biomechanical perspective.
View Article and Find Full Text PDFRegulation of Ebola GP conformation and membrane binding by the chemical environment of the late endosome.
PLoS Pathog
December 2023
Department of Microbiology and Physiological Systems, UMass Chan Medical School, Worcester, Massachusetts, United States of America.
Interaction between the Ebola virus envelope glycoprotein (GP) and the endosomal membrane is an essential step during virus entry into the cell. Acidic pH and Ca2+ have been implicated in mediating the GP-membrane interaction. However, the molecular mechanism by which these environmental factors regulate the conformational changes that enable engagement of GP with the target membrane is unknown.
View Article and Find Full Text PDFAntiviral drugs targeting endosomal membrane proteins inhibit distant animal and human pathogenic viruses.
Antiviral Res
February 2021
Dpt. Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Ctra. de la Coruña Km 7.5, 28040, Madrid, Spain. Electronic address:
The endocytic pathway is a common strategy that several highly pathogenic viruses use to enter into the cell. To demonstrate the usefulness of this pathway as a common target for the development of broad-spectrum antivirals, the inhibitory effect of drug compounds targeting endosomal membrane proteins were investigated. This study entailed direct comparison of drug effectiveness against animal and human pathogenic viruses, namely Ebola (EBOV), African swine fever virus (ASFV), and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
View Article and Find Full Text PDFTransfer functions linking neural calcium to single voxel functional ultrasound signal.
Nat Commun
June 2020
INSERM U1128, Laboratory of Neurophysiology and New Microscopy, Université de Paris, Paris, France.
Functional ultrasound imaging (fUS) is an emerging technique that detects changes of cerebral blood volume triggered by brain activation. Here, we investigate the extent to which fUS faithfully reports local neuronal activation by combining fUS and two-photon microscopy (2PM) in a co-registered single voxel brain volume. Using a machine-learning approach, we compute and validate transfer functions between dendritic calcium signals of specific neurons and vascular signals measured at both microscopic (2PM) and mesoscopic (fUS) levels.
View Article and Find Full Text PDFConformational changes in the Ebola virus membrane fusion machine induced by pH, Ca2+, and receptor binding.
PLoS Biol
February 2020
Department of Molecular Biology and Microbiology, Tufts University School of Medicine and Sackler School of Graduate Biomedical Sciences, Boston, Massachusetts, United States of America.
The Ebola virus (EBOV) envelope glycoprotein (GP) is a membrane fusion machine required for virus entry into cells. Following endocytosis of EBOV, the GP1 domain is cleaved by cellular cathepsins in acidic endosomes, removing the glycan cap and exposing a binding site for the Niemann-Pick C1 (NPC1) receptor. NPC1 binding to cleaved GP1 is required for entry.
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