Searching the Resource Information Network
Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.
Enteroviruses (EVs) comprise a large genus of positive-sense, single-stranded RNA viruses whose members cause a number of important and widespread human diseases, including poliomyelitis, myocarditis, acute flaccid myelitis and the common cold. How EVs co-opt cellular functions to promote replication and spread is incompletely understood. Here, using genome-scale CRISPR screens, we identify the actin histidine methyltransferase SET domain containing 3 (SETD3) as critically important for viral infection by a broad panel of EVs, including rhinoviruses and non-polio EVs increasingly linked to severe neurological disease such as acute flaccid myelitis (EV-D68) and viral encephalitis (EV-A71). We show that cytosolic SETD3, independent of its methylation activity, is required for the RNA replication step in the viral life cycle. Using quantitative affinity purification-mass spectrometry, we show that SETD3 specifically interacts with the viral 2A protease of multiple enteroviral species, and we map the residues in 2A that mediate this interaction. 2A mutants that retain protease activity but are unable to interact with SETD3 are severely compromised in RNA replication. These data suggest a role of the viral 2A protein in RNA replication beyond facilitating proteolytic cleavage. Finally, we show that SETD3 is essential for in vivo replication and pathogenesis in multiple mouse models for EV infection, including CV-A10, EV-A71 and EV-D68. Our results reveal a crucial role of a host protein in viral pathogenesis, and suggest targeting SETD3 as a potential mechanism for controlling viral infections.
Pubmed ID: 31527793
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Software package as multiple sequence alignment tool that uses seeded guide trees and HMM profile-profile techniques to generate alignments between three or more sequences. Accepts nucleic acid or protein sequences in multiple sequence formats NBRF/PIR, EMBL/UniProt, Pearson (FASTA), GDE, ALN/Clustal, GCG/MSF, RSF.
View all literature mentionsNon-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsCommercial instrument and chemical vendor. Developer and manufacturer of specialized technological products for life science research and clinical diagnostics markets.
View all literature mentionsA complete, high-capacity centralized gene expression analysis system, developed in response to the needs of a distributed user community.
View all literature mentionsCompany provides laboratories worldwide with analytical instruments and supplies, clinical and diagnostic testing services, consumables, applications and expertise in life sciences and applied chemical markets.
View all literature mentionsSoftware tool as Windows client application for targeted proteomics method creation and quantitative data analysis. Open source document editor for creating and analyzing targeted proteomics experiments. Used for large scale quantitative mass spectrometry studies in life sciences.
View all literature mentionsA quantitative proteomics software package for analyzing large-scale mass-spectrometric data sets. It is a set of algorithms that include peak detection and scoring of peptides, mass calibration, database searches for protein identification, protein quantification, and provides summary statistics.
View all literature mentionsGraph-based alignment of next generation sequencing reads to a population of genomes.
View all literature mentionsFluorospectrometer for broad spectrum fluorescence analysis. It uses as little as 1 μL of sample volume and lowers the mass detection limit more than an order of magnitude.
View all literature mentionsCell line HEK293-FT is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Huh-7.5.1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line BHK-21 is a Spontaneously immortalized cell line with a species of origin Mesocricetus auratus (Golden hamster)
View all literature mentionsCell line C6/36 is a Spontaneously immortalized cell line with a species of origin Aedes albopictus (Asian tiger mosquito)
View all literature mentionsCell line HEK293-FT is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Huh-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentions