Biology subjects

Suter, C.

Publications and source records attributed to Suter, C..

5 recordsLinked to original sources

bioRxiv2026

Transferrin receptor 1 binds human parvovirus B19 VP1u to facilitate entry

Human parvovirus B19 (B19V) exhibits a strict tropism for erythroid progenitor cells, which is governed by the VP1 unique region (VP1u). This region mediates cell-specific uptake by interacting with an unknown cellular receptor, termed VP1uR. Proximity labeling in permissive erythroid cells identified transferrin receptor 1 (TfR1/CD71) as the predominant membrane protein associated with VP1u. VP1u constructs colocalized with TfR1 at the cell surface of erythroid cells. Incubation with anti-TfR1 antibody OKT9 abolished binding and uptake of recombinant VP1u. While OKT9 efficiently inhibited B19V uptake and infection, it did not block virus binding to host cells. Direct binding assays confirmed interaction of VP1u to human TfR1. Using cryoEM we solved the 2.4 [A] structure of the TfR1-VP1u complex, mapping the binding site and identifying the specific interactions. These findings establish TfR1 as the previously unknown receptor, VP1uR, required for B19V uptake.

microbiology↗

bioRxiv2025

Cellular determinants of parvovirus B19 infection in the human placenta

Parvovirus B19 (B19V) is a prevalent human pathogen that can cross the placenta by a mechanism that remains unknown, posing a risk of severe fetal complications, particularly during the first trimester of pregnancy. We investigated the expression of B19V-specific receptors in the three trophoblast cell types, cytotrophoblasts (CTBs), syncytiotrophoblasts (STBs), and extravillous trophoblasts (EVTs), and assessed their susceptibility to infection. VP1uR, the erythroid-specific receptor that mediates viral uptake and infection in erythroid progenitor cells, is expressed in CTBs and STBs, but not in EVTs. Globoside, a glycosphingolipid that is essential for the escape of the virus from endosomes, is also expressed in these cells, except for choriocarcinoma-derived CTBs. In the latter, the absence of globoside can be overcome by promoting endosomal leakage with polyethyleneimine. While erythropoietin receptor (EpoR) signaling is associated with the strict erythroid tropism of B19V, it is not required for infection in trophoblasts. Transfection experiments revealed that highly proliferative first-trimester CTBs are more permissive to B19V infection than the low-proliferative CTBs from term placenta. These findings demonstrate that B19V targets and infects specific trophoblast cells, where viral entry and replication are collectively mediated by VP1uR, globoside, and high cellular proliferative activity, but are independent of EpoR signaling. HighlightsO_LITrophoblasts express the specific receptors necessary for B19V entry. C_LIO_LISusceptibility and permissiveness to B19V vary by trophoblast subtype and gestational age. C_LIO_LIHighly proliferative first-trimester cytotrophoblasts show increased permissiveness to B19V. C_LIO_LIB19V infection in trophoblasts depends on globoside but is independent of EpoR signaling. C_LI

microbiology↗

bioRxiv2024

Globoside is an essential intracellular factor required for parvovirus B19 endosomal escape in erythroid progenitor cells

Human parvovirus B19 (B19V), like most parvoviruses, possesses phospholipase A2 (PLA2) activity, which is thought to mediate endosomal escape by membrane disruption. Here, we challenge this model and find evidence for a mechanism of B19V entry mediated by the glycosphingolipid globoside without endosome disruption and retrograde transport to the Golgi. We show that B19V PLA2 activity requires specific calcium levels and pH conditions that are not optimal in endosomes. Accordingly, endosomal membrane integrity was maintained during B19V entry. Furthermore, endosomes remained intact when loaded with MS2 bacteriophage particles pseudotyped with multiple B19V PLA2 subunits, providing superior enzymatic potential compared to native B19V. In globoside knockout cells, incoming viruses are arrested in the endosomal compartment and the infection is blocked. Infection can be rescued by promoting endosomal leakage with polyethyleneimine (PEI), demonstrating the essential role of globoside in facilitating endosomal escape. Incoming virus colocalizes with Golgi markers and interfering with Golgi function blocks infection, suggesting that globoside-mediated entry involves the Golgi compartment, which provides conditions favorable for the lipolytic PLA2. Our study challenges the current model of B19V entry and identifies globoside as an essential intracellular receptor required for endosomal escape.

microbiology↗

bioRxiv2023

Globoside and the mucosal pH mediate parvovirus B19 entry through the epithelial barrier

Parvovirus B19 (B19V) is transmitted primarily via the respiratory route, however, the mechanism involved remains unknown. B19V targets a restricted receptor expressed in erythroid progenitor cells in the bone marrow. However, B19V shifts the receptor under acidic conditions and targets the widely expressed globoside. The pH-dependent interaction with globoside may allow virus entry through the naturally acidic nasal mucosa. To test this hypothesis, MDCK II cells and well-differentiated human airway epithelial cell (hAEC) cultures were grown on porous membranes and used as models to study the interaction of B19V with the epithelial barrier. Globoside expression was detected in polarized MDCK II cells and the ciliated cell population of well-differentiated hAEC cultures. Under the acidic conditions of the nasal mucosa, virus attachment and transcytosis occurred without productive infection. Neither virus attachment nor transcytosis was observed under neutral pH conditions or in globoside knockout cells, demonstrating the concerted role of globoside and acidic pH in the transcellular transport of B19V. Globoside-dependent virus uptake involved VP2 and occurred by a clathrin-independent pathway that is cholesterol and dynamin-dependent. This study provides mechanistic insight into the transmission of B19V through the respiratory route and reveals novel vulnerability factors of the epithelial barrier to viruses. Author summaryThe mechanism of entry of parvovirus B19 through the respiratory epithelium remains elusive. By using polarized MDCK II and well-differentiated primary human airway epithelial cell cultures, we revealed that the virus exploits the natural acidic environment of the nasal mucosa and the expression of globoside in the ciliated cell population of the airway to breach the respiratory epithelium by transcytosis. Mechanistically, virus entry and intracellular trafficking in the epithelial cells differ substantially from that in the permissive erythroid progenitor cells.

microbiology↗

bioRxiv2018

Deep sequencing of circulating exosomal microRNA allows non-invasive glioblastoma diagnosis

Exosomes are nano-sized extracellular vesicles released by many cells that contain molecules characteristic of their cell-of-origin, including microRNA. Exosomes released by glioblastoma cross the blood-brain-barrier into the peripheral circulation, and carry molecular cargo distinct to that of free-circulating miRNA. In this pilot study, serum exosomal-microRNAs were isolated from glioblastoma (n=12) patients and analyzed using unbiased deep sequencing. Results were compared to sera from age- and gender-matched healthy controls, and to grades II-III (n=10) glioma patients. Significant differentially expressed microRNAs were identified, and the predictive power of individual and subsets of microRNAs were tested using univariate and multivariate analyses. Additional sera from glioblastoma patients (n=4) and independent sets of healthy (n=9) and non-glioma (n=10) controls were used to further test the specificity and predictive power of this unique exosomal-microRNA signature. Twenty-six microRNAs were differentially expressed in serum exosomes from glioblastoma patients relative to healthy controls. Random forest modeling and data partitioning selected seven miRNAs (miR-182-5p, miR-328-3p, miR-339-5p, miR-340-5p, miR-485-3p, miR-486-5p and miR-543) as the most stable for classifying glioblastoma. Strikingly, within this model, six iterations of these miRNA classifiers could distinguish glioblastoma patients from controls with perfect accuracy. The seven-miRNA panel was able to correctly classify all specimens in validation cohorts (n=23). Also identified were 23 dysregulated miRNAs in IDHMUT gliomas, a partially overlapping yet distinct signature of lower grade glioma. Serum exosomal-miRNA signatures can accurately diagnose glioblastoma preoperatively. miRNA signatures identified are distinct from previously reported free-circulating miRNA studies in GBM patients, and appear to be superior.

pathology↗