{"doi":"10.1073/pnas.2016650117","title":"SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling","abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic that is a serious global health problem. Evasion of IFN-mediated antiviral signaling is a common defense strategy that pathogenic viruses use to replicate and propagate in their host. In this study, we show that SARS-CoV-2 is able to efficiently block STAT1 and STAT2 nuclear translocation in order to impair transcriptional induction of IFN-stimulated genes (ISGs). Our results demonstrate that the viral accessory protein Orf6 exerts this anti-IFN activity. We found that SARS-CoV-2 Orf6 localizes at the nuclear pore complex (NPC) and directly interacts with Nup98-Rae1 via its C-terminal domain to impair docking of cargo-receptor (karyopherin/importin) complex and disrupt nuclear import. In addition, we show that a methionine-to-arginine substitution at residue 58 impairs Orf6 binding to the Nup98-Rae1 complex and abolishes its IFN antagonistic function. All together our data unravel a mechanism of viral antagonism in which a virus hijacks the Nup98-Rae1 complex to overcome the antiviral action of IFN.","journal":"Proceedings of the National Academy of Sciences","year":2020,"id":48080,"datarank":0.9534161491043839,"base_score":6.3561076606958915,"endowment":6.3561076606958915,"self_citation_contribution":0.9534161491043839,"citation_network_contribution":0.0,"self_endowment_contribution":0.9534161491043839,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":575,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":2383,"name":"Thomas Kehrer","orcid":"0000-0002-6433-0098","position":1,"is_corresponding":false},{"id":225546,"name":"María Teresa Sánchez-Aparicio","orcid":"0000-0001-6556-5924","position":2,"is_corresponding":false},{"id":225547,"name":"Ke Zhang","orcid":"0000-0001-5365-3142","position":3,"is_corresponding":false},{"id":225548,"name":"Phillip Cohen","orcid":"0000-0002-9368-5154","position":4,"is_corresponding":false},{"id":225549,"name":"Roosheel S. Patel","orcid":"0000-0002-0683-6920","position":5,"is_corresponding":false},{"id":2417,"name":"Anastasija Čupić","orcid":"0000-0002-1291-1042","position":6,"is_corresponding":false},{"id":229253,"name":"Tadashi Makio","orcid":null,"position":7,"is_corresponding":false},{"id":225550,"name":"Menghan Mei","orcid":"0000-0001-7130-4659","position":8,"is_corresponding":false},{"id":103645,"name":"Elena Moreno","orcid":"0000-0002-2301-4558","position":9,"is_corresponding":false},{"id":109626,"name":"Oded Danziger","orcid":"0000-0003-0533-3851","position":10,"is_corresponding":false},{"id":1481,"name":"Kris M. White","orcid":"0000-0003-0889-0506","position":11,"is_corresponding":false},{"id":107922,"name":"Raveen Rathnasinghe","orcid":"0000-0002-1260-2493","position":12,"is_corresponding":false},{"id":225551,"name":"Melissa B. Uccellini","orcid":"0000-0003-2589-4824","position":13,"is_corresponding":false},{"id":225552,"name":"Shengyan Gao","orcid":"0000-0002-1281-8753","position":14,"is_corresponding":false},{"id":104923,"name":"Teresa Aydillo","orcid":"0000-0003-3086-1058","position":15,"is_corresponding":false},{"id":2386,"name":"Ignacio Mena","orcid":"0000-0001-5464-7086","position":16,"is_corresponding":false},{"id":106551,"name":"Xin Yin","orcid":"0000-0003-2357-6718","position":17,"is_corresponding":false},{"id":107909,"name":"Laura Martin‐Sancho","orcid":"0000-0003-1489-2815","position":18,"is_corresponding":false},{"id":1363,"name":"Nevan J. Krogan","orcid":"0000-0003-4902-337X","position":19,"is_corresponding":false},{"id":68656,"name":"Sumit K. Chanda","orcid":"0000-0001-9399-7927","position":20,"is_corresponding":false},{"id":107923,"name":"Michael Schotsaert","orcid":"0000-0003-3156-3132","position":21,"is_corresponding":false},{"id":225553,"name":"Richard W. 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