Viral infection is an intricate process that requires the concerted action of both viral and host cell components. Entry of viruses into cells is initiated by interactions between viral proteins and their cell surface receptors. Despite recent progress, the molecular mechanisms underlying the multistep reovirus entry process are poorly understood. Using atomic force microscopy, we investigated how the reovirus σ1 attachment protein binds to both α-linked sialic acid (α-SA) and JAM-A cell-surface receptors. We discovered that initial σ1 binding to α-SA favors a strong multivalent anchorage to JAM-A. The enhanced JAM-A binding by virions following α-SA engagement is comparable to JAM-A binding by infectious subvirion particles (ISVPs) in the absence of α-SA. Since ISVPs have an extended σ1 conformer, this finding suggests that α-SA binding triggers a conformational change in σ1. These results provide new insights into the function of viral attachment proteins in the initiation of infection and open new avenues for the use of reoviruses as oncolytic agents.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773860 | PMC |
| http://dx.doi.org/10.1038/s41467-019-12411-2 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cellular adhesion molecules in drug-naïve and previously medicated patients with schizophrenia-spectrum disorders.
Schizophr Res
May 2024
Department of Clinical Medicine (K1), University of Bergen, Bergen, Norway; NORMENT Centre of Excellence, Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
Background: Endothelial inflammation may be involved in the pathogenesis of schizophrenia, and cellular adhesion molecules (CAMs) on endothelial cells may facilitate leukocyte binding and transendothelial migration of cells and inflammatory factors. The aim of the present study was to assess levels of soluble cellular adhesion molecules, including intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, mucosal addressin cell adhesion molecule (MADCAM), junctional adhesion molecule (JAM-A) and neural cadherin (N-CAD) in patients with schizophrenia compared to healthy controls.
Methods: The study population consists of 138 patients with schizophrenia-spectrum disorder, of whom 54 were drug-naïve, compared to 317 general population controls.
The Role of ZO-2 in Modulating JAM-A and γ-Actin Junctional Recruitment, Apical Membrane and Tight Junction Tension, and Cell Response to Substrate Stiffness and Topography.
Int J Mol Sci
February 2024
Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies (Cinvestav), Mexico City 07360, Mexico.
This work analyzes the role of the tight junction (TJ) protein ZO-2 on mechanosensation. We found that the lack of ZO-2 reduced apical membrane rigidity measured with atomic force microscopy, inhibited the association of γ-actin and JAM-A to the cell border, and instead facilitated p114RhoGEF and afadin accumulation at the junction, leading to an enhanced mechanical tension at the TJ measured by FRET, with a ZO-1 tension probe, and increased tricellular TJ tension. Simultaneously, adherens junction tension measured with an E-cadherin probe was unaltered.
View Article and Find Full Text PDFIntercellular adhesion complexes must withstand mechanical forces to maintain tissue cohesion, while also retaining the capacity for dynamic remodeling during tissue morphogenesis and repair. Most cell-cell adhesion complexes contain at least one PSD95/Dlg/ZO-1 (PDZ) domain situated between the adhesion molecule and the actin cytoskeleton. However, PDZ-mediated interactions are characteristically nonspecific, weak, and transient, with several binding partners per PDZ domain, micromolar dissociation constants, and bond lifetimes of seconds or less.
View Article and Find Full Text PDFDysfunction of the intestinal physical barrier in the intestinal inflammation of tongue sole, Cynoglossus semilaevis, induced by Shewanella algae infection.
Fish Shellfish Immunol
August 2023
Tianjin Key Lab of Aqua-ecology and Aquaculture, Fisheries College, Tianjin Agricultural University, Tianjin, 300384, China. Electronic address:
Article Synopsis
- Bacterial intestinal inflammation is a common issue in cultured fish, specifically in tongue sole (Cynoglossus semilaevis), which was studied after exposure to Shewanella algae.
- The research revealed significant changes in intestinal permeability, highlighted by wider intercellular spaces and an increase in mucous cells following the infection.
- Key inflammatory cytokines showed increased expression, while important tight junction molecules and keratins decreased, indicating a complex relationship between infection and intestinal barrier dysfunction.
Deciphering molecular mechanisms stabilizing the reovirus-binding complex.
Proc Natl Acad Sci U S A
May 2023
Louvain Institute of Biomolecular Science and Technology, NanoBiophysics lab, Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium.
Mammalian orthoreoviruses (reoviruses) serve as potential triggers of celiac disease and have oncolytic properties, making these viruses potential cancer therapeutics. Primary attachment of reovirus to host cells is mainly mediated by the trimeric viral protein, σ1, which engages cell-surface glycans, followed by high-affinity binding to junctional adhesion molecule-A (JAM-A). This multistep process is thought to be accompanied by major conformational changes in σ1, but direct evidence is lacking.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!