Identification of Residues in Lassa Virus Glycoprotein Subunit 2 That Are Critical for Protein Function.
Reads0
Chats0
TLDR
The data suggest these residues are critical for GP2 function in LASV entry, and seven GP2 mutants that were cleaved efficiently but were unable to effectively transduce cells are identified.Abstract:
Lassa virus (LASV) is an Old World arenavirus, endemic to West Africa, capable of causing hemorrhagic fever. Currently, there are no approved vaccines or effective antivirals for LASV. However, thorough understanding of the LASV glycoprotein and entry into host cells could accelerate therapeutic design. LASV entry is a two-step process involving the viral glycoprotein (GP). First, the GP subunit 1 (GP1) binds to the cell surface receptor and the viral particle is engulfed into an endosome. Next, the drop in pH triggers GP rearrangements, which ultimately leads to the GP subunit 2 (GP2) forming a six-helix-bundle (6HB). The process of GP2 forming 6HB fuses the lysosomal membrane with the LASV envelope, allowing the LASV genome to enter the host cell. The aim of this study was to identify residues in GP2 that are crucial for LASV entry. To achieve this, we performed alanine scanning mutagenesis on GP2 residues. We tested these mutant GPs for efficient GP1-GP2 cleavage, cell-to-cell membrane fusion, and transduction into cells expressing α-dystroglycan and secondary LASV receptors. In total, we identified seven GP2 mutants that were cleaved efficiently but were unable to effectively transduce cells: GP-L280A, GP-L285A/I286A, GP-I323A, GP-L394A, GP-I403A, GP-L415A, and GP-R422A. Therefore, the data suggest these residues are critical for GP2 function in LASV entry.read more
Citations
More filters
Journal ArticleDOI
Bacteria from the Genus Arcobacter Are Abundant in Effluent from Wastewater Treatment Plants.
TL;DR: It is shown that the removal of species in the genus Arcobacter was less effective than for many other abundant genera in the influent wastewater, and there is an urgent need for new standardized culture-independent measurements of pathogens in effluent wastewaters.
Journal ArticleDOI
Hemorrhagic Fever-Causing Arenaviruses: Lethal Pathogens and Potent Immune Suppressors.
Morgan E. Brisse,Hinh Ly +1 more
TL;DR: Current knowledge about arenaviral evolution, ecology, transmission patterns, life cycle, modulation of host immunity, disease pathogenesis, as well as discusses recent development of preventative and therapeutic pursuits against this group of deadly viral pathogens are synthesized.
Journal ArticleDOI
Mechanisms of fungal dissemination
Ashley B. Strickland,Meiqing Shi +1 more
TL;DR: A review of the current understanding of how fungi disseminate from the initial infection sites to the bloodstream, how immune cells eliminate fungi from circulation and how fungi leave the blood and enter distant organs, highlighting some recent advances and offering some perspectives on future directions as mentioned in this paper.
Journal ArticleDOI
Oral Dysbiosis and Autoimmunity: From Local Periodontal Responses to an Imbalanced Systemic Immunity. A Review
TL;DR: The autoimmune mechanisms related to periodontitis physio-pathogenesis and the participation of oral dysbiosis on local periodontal autoimmune responses as well as on different systemic inflammatory diseases are discussed.
Journal ArticleDOI
Intestinal microbiota and its interaction to intestinal health in nursery pigs
Marcos E Duarte,Sung Woo Kim +1 more
TL;DR: It was demonstrated that the mucosa-associated microbiota should be evaluated when analyzing the interaction among diets, microbiota, and health, and supplementation of feed additives aimed to promote the intestinal health of pigs should consider their roles in the modulation of mucosa -associated microbiota as biomarkers to predict the response of growth performance to dietary interventions.
References
More filters
Journal ArticleDOI
Lysosomal Acidification Mechanisms
TL;DR: Both the V-ATPase and the counterion transporter are likely to be important players in the mechanisms determining the steady-state pH of the lysosome interior.
Journal ArticleDOI
Structures and mechanisms of viral membrane fusion proteins: multiple variations on a common theme.
TL;DR: Viral fusion proteins convert from a fusion-competent state to a membrane-embedded homotrimeric prehairpin, and then to a trimer-of-hairpins that brings the fusion peptide and the transmembrane domain into close proximity thereby facilitating the union of viral and target membranes.
Journal ArticleDOI
Lipid landscapes and pipelines in membrane homeostasis
TL;DR: This work reviews recent insights into the molecular basis of this regulatory network and considers examples in which malfunction of its components leads to system failure and disease.
Journal ArticleDOI
Identification of α-dystroglycan as a receptor for lymphocytic choriomeningitis virus and Lassa fever virus
Wei Cao,Michael D. Henry,Persephone Borrow,Hiroki Yamada,John H. Elder,Eugene V. Ravkov,Stuart T. Nichol,Richard W. Compans,Kevin P. Campbell,Michael B. A. Oldstone +9 more
TL;DR: A peripheral membrane protein that is interactive with lymphocytic choriomeningitis virus (LCMV) was purified from cells permissive to infection and determined to be alpha-dystroglycan (alpha-DG).
Journal ArticleDOI
Measles Viruses on Throat Swabs from Measles Patients Use Signaling Lymphocytic Activation Molecule (CDw150) but Not CD46 as a Cellular Receptor
TL;DR: The results strongly suggest that the viruses in the bodies of measles patients use SLAM but probably not CD46 as a cellular receptor.