{"doi":"10.1101/2021.06.07.447466","title":"eIF2B-capturing viral protein NSs suppresses the integrated stress response","abstract":"SUMMARY Various stressors such as viral infection lead to the suppression of cap-dependent translation and the activation of the integrated stress response (ISR), since the stress-induced phosphorylated eukaryotic translation initiation factor 2 [eIF2(αP)] tightly binds to eIF2B to prevent it from exchanging guanine nucleotides on unphosphorylated eIF2. Sandfly fever Sicilian virus (SFSV) evades this cap-dependent translation suppression through the interaction between its nonstructural protein NSs and host eIF2B. Our cryo-electron microscopy (cryo-EM) analysis revealed that SFSV NSs binds to the α-subunit of eIF2B in a competitive manner with eIF2(αP). Together with SFSV NSs, eIF2B exhibits normal nucleotide exchange activity even in the presence of eIF2(αP). A genome-wide ribosome profiling analysis clarified that SFSV NSs in human cultured cells attenuates the ISR. Furthermore, SFSV NSs exhibited neuroprotective effects against the ISR-inducing stress. Since the ISR inhibition is beneficial in various neurological disease models, SFSV NSs is promising as a therapeutic ISR inhibitor.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":221058,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":245404,"name":"Yuichi Shichino","orcid":"0000-0002-0093-1185","position":1,"is_corresponding":false},{"id":292898,"name":"Tatsuya Osaki","orcid":"0000-0001-7174-0629","position":2,"is_corresponding":false},{"id":554459,"name":"Ayako Sakamoto","orcid":"0000-0002-9040-429X","position":3,"is_corresponding":false},{"id":554460,"name":"Madoka Nishimoto","orcid":"0000-0003-0948-2504","position":4,"is_corresponding":false},{"id":287606,"name":"Mari Takahashi","orcid":"0000-0002-9995-0019","position":5,"is_corresponding":false},{"id":236031,"name":"Mari Mito","orcid":"0000-0003-2564-6273","position":6,"is_corresponding":false},{"id":287578,"name":"Friedemann Weber","orcid":"0000-0001-9737-337X","position":7,"is_corresponding":false},{"id":292903,"name":"Yoshiho Ikeuchi","orcid":"0000-0002-2829-3840","position":8,"is_corresponding":false},{"id":17833,"name":"Shintaro Iwasaki","orcid":"0000-0001-7724-3754","position":9,"is_corresponding":false},{"id":287609,"name":"Takuhiro Ito","orcid":"0000-0003-3704-5205","position":10,"is_corresponding":false},{"id":554456,"name":"Kazuhiro Kashiwagi","orcid":"0000-0001-6470-5817","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T23:53:50.838581Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}