ArticlePLoS pathogens2021
Heparan sulfate proteoglycans serve as alternative receptors for low affinity LCMV variants.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- The essential role of heparan sulfate in the entry of PDCoV and other porcine coronaviruses.Virulence · 2026Article
- Investigating CD8 T Cell Exhaustion in Chronic LCMV Infection by Flow Cytometry.Current protocols · 2026Article
- Challenges in developing broad-spectrum viral attachment inhibitors targeting heparan sulfates and sialic acids.Journal of virology · 2026Review
- Sulfated glycosaminoglycans inhibit LCMV entry and modulate antiviral immunity and pathology.EMBO molecular medicine · 2026Article
- The oncolytic vesicular stomatitis virus VSV-GP shows profound oncolytic activity in NUT-carcinoma cell lines.Molecular therapy. Oncology · 2026Article
- Meta-analysis of functional genomics studies reveals conserved cellular pathways required by viruses of pandemic concern.Access microbiology · 2026Article
- Optimized arenaviruses with tumor-tropic mutations promote safe anti-tumor efficacy via sustainable immune modulatory properties.Cell reports. Medicine · 2025Article
- Interleukin-12 encoded by the oncolytic virus VSV-GP enhances therapeutic antitumor efficacy by inducing CD8+ T-cell responses with a long-lived effector cell phenotype.Journal for immunotherapy of cancer · 2025Article
- Genome-wide identification of modulators of Chlamydia trachomatis parasitophorous vacuole stability highlights an important role for sphingolipid supply.PLoS biology · 2025Article
- Lymph-Node Inspired Hydrogels Enhance CAR Expression and Proliferation of CAR T Cells.ACS applied materials & interfaces · 2025Article
- Lassa virus protein-protein interactions as mediators of Lassa fever pathogenesis.Virology journal · 2025Review
- High-Affinity-Mediated Viral Entry Triggers Innate Affinity Escape Resulting in Type I IFN Resistance and Impaired T Cell Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- The underlying mechanisms of arenaviral entry through matriglycan.Frontiers in molecular biosciences · 2024Review
- Differential regulation of heparan sulfate biosynthesis in fibroblasts cocultured with normal vs. cancerous prostate cells.Frontiers in immunology · 2024Article
- Structural basis for antibody-mediated neutralization of lymphocytic choriomeningitis virus.Cell chemical biology · 2023Article
- Arenaviruses: Old viruses present new solutions for cancer therapy.Frontiers in immunology · 2023Review
- Replicating-Competent VSV-Vectored Pseudotyped Viruses.Advances in experimental medicine and biology · 2023Article
- Pseudotyped Viruses for Mammarenavirus.Advances in experimental medicine and biology · 2023Article
- Article
- CD164 is a host factor for lymphocytic choriomeningitis virus entry.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Members of the Old World Arenaviruses primarily utilize α-dystroglycan (α-DAG1) as a cellular receptor for infection. Mutations within the glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV) reduce or abrogate the binding affinity to α-DAG1 and thus influence viral persistence, kinetics, and cell tropism. The observation that α-DAG1 deficient cells are still highly susceptible to low affinity variants, suggests the use of an alternative receptor(s). In this study, we used a genome-wide CRISPR Cas9 knockout screen in DAG1 deficient 293T cells to identify host factors involved in α-DAG1-independent LCMV infection. By challenging cells with vesicular stomatitis virus (VSV), pseudotyped with the GP of LCMV WE HPI (VSV-GP), we identified the heparan sulfate (HS) biosynthesis pathway as an important host factor for low affinity LCMV infection. These results were confirmed by a genetic approach targeting EXTL3, a key factor in the HS biosynthesis pathway, as well as by enzymatic and chemical methods. Interestingly, a single point mutation within GP1 (S153F or Y155H) of WE HPI is sufficient for the switch from DAG1 to HS binding. Furthermore, we established a simple and reliable virus-binding assay, using directly labelled VSV-GP by intramolecular fusion of VSV-P and mWasabi, demonstrating the importance of HS for virus attachment but not entry in Burkitt lymphoma cells after reconstitution of HS expression. Collectively, our study highlights the essential role of HS for low affinity LCMV infection in contrast to their high affinity counterparts. Residual LCMV infection in double knockouts indicate the use of (a) still unknown entry receptor(s).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.