SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling.
Lisa Miorin,Thomas Kehrer,Maria Teresa Sánchez-Aparicio,Ke Zhang,Phillip Cohen,Roosheel S. Patel,Anastasija Cupic,Tadashi Makio,Menghan Mei,Elena Moreno,Oded Danziger,Kris M. White,Raveen Rathnasinghe,Melissa B. Uccellini,Shengyan Gao,Teresa Aydillo,Ignacio Mena,Xin Yin,Laura Martin-Sancho,Nevan J. Krogan,Nevan J. Krogan,Nevan J. Krogan,Sumit K. Chanda,Michael Schotsaert,Richard W. Wozniak,Yi Ren,Brad R. Rosenberg,Beatriz M. A. Fontoura,Adolfo García-Sastre +28 more
Reads0
Chats0
TLDR
SARS-CoV-2 is able to efficiently block STAT1 and STAT2 nuclear translocation in order to impair transcriptional induction of IFN-stimulated genes (ISGs).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.read more
Citations
More filters
Journal ArticleDOI
Insight into the emerging role of SARS-CoV-2 nonstructural and accessory proteins in modulation of multiple mechanisms of host innate defense.
Abualgasim Elgaili Abdalla,Jianping Xie,Kashaf Junaid,Sonia Younas,Tilal Elsaman,Khalid Omer Abdalla Abosalif,Ayman Ali Mohammed Alameen,Mahjoob Osman Mahjoob,Mohammed Yagoub Mohammed Elamir,Hasan Ejaz +9 more
TL;DR: In this article, the authors describe the complex molecular interplay of SARS-CoV-2 NSPs and accessory proteins with the host's signaling mediating immune evasion, and discuss the crucial role played by immunomodulation therapy to address immune evasion.
Journal ArticleDOI
The Pathogenic Features of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Possible Mechanisms for Immune Evasion?
TL;DR: The aim of this review was to summarize and sort dozens of published studies on PubMed to explore the pathogenic features of SARS-CoV-2, as well as the possible immune escape mechanisms of this virus.
Posted ContentDOI
The SARS-CoV-2 protein ORF3c is a mitochondrial modulator of innate immunity
Hazel Stewart,Yongxu Lu,Sarah O'Keefe,Anusha Valpadashi,Luis Daniel Cruz-Zaragoza,Hendrik A. Michel,Samantha K. Nguyen,George Carnell,Nina I. Lukhovitskaya,Rachel Milligan,Irwin Jungreis,Valeria Lulla,Andrew D. Davidson,David A. Matthews,Stephen High,Peter Rehling,Edward Emmott,Jonathan L. Heeney,James R. Edgar,Geoffrey Smith,Andrew E. Firth +20 more
TL;DR: In this article , the authors showed that ORF3c localises to mitochondria during infection, where it inhibits innate immunity by restricting IFN-β production, but not NF-κB activation or JAK-STAT signalling downstream of type I IFN stimulation.
Posted ContentDOI
Unambiguous detection of SARS-CoV-2 subgenomic mRNAs with single cell RNA sequencing (preprint)
TL;DR: In this article, a single cell CoronaVirus sequencing (scCoVseq) method was proposed to quantify and detect SARS-CoV-2 RNAs with a focus on subgenomic mRNAs (sgmRNAs) produced only during active viral replication and not present in viral particles.
Journal ArticleDOI
Temporal changes in the accessory protein mutations of SARS‐CoV‐2 variants and their predicted structural and functional effects
TL;DR: Among the accessory proteins, ORF6 and ORF8 were highlighted because of their strong and weak correlation with Spike protein mutations, respectively, and are good candidates for further experimental evaluation.
References
More filters
Journal ArticleDOI
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Peng Zhou,Xing-Lou Yang,Xian Guang Wang,Ben Hu,Lei Zhang,Wei Zhang,Hao Rui Si,Yan Zhu,Bei Li,Chao Lin Huang,Hui-Dong Chen,Jing Chen,Yun Luo,Hua Guo,Ren Di Jiang,Meiqin Liu,Ying Chen,Xu Rui Shen,Xi Wang,Xiao Shuang Zheng,Kai Zhao,Quanjiao Chen,Fei Deng,Lin Lin Liu,Bing Yan,Fa Xian Zhan,Yan-Yi Wang,Gengfu Xiao,Zhengli Shi +28 more
TL;DR: Identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China, and it is shown that this virus belongs to the species of SARSr-CoV, indicates that the virus is related to a bat coronav virus.
Journal ArticleDOI
Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding.
Roujian Lu,Xiang Zhao,Juan Li,Peihua Niu,Bo Yang,Honglong Wu,Wenling Wang,Hao Song,Baoying Huang,Na Zhu,Yuhai Bi,Xuejun Ma,Faxian Zhan,Liang Wang,Tao Hu,Hong Zhou,Zhenhong Hu,Weimin Zhou,Li Zhao,Jing Chen,Yao Meng,Ji Wang,Yang Lin,Jianying Yuan,Zhihao Xie,Jinmin Ma,William J. Liu,Dayan Wang,Wenbo Xu,Edward C. Holmes,George F. Gao,George F. Gao,Guizhen Wu,Weijun Chen,Weifeng Shi,Wenjie Tan,Wenjie Tan +36 more
TL;DR: The phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans.
Journal ArticleDOI
Comprehensive Integration of Single-Cell Data.
Tim Stuart,Andrew Butler,Paul J. Hoffman,Christoph Hafemeister,Efthymia Papalexi,William M. Mauck,Yuhan Hao,Marlon Stoeckius,Peter Smibert,Rahul Satija +9 more
TL;DR: A strategy to "anchor" diverse datasets together, enabling us to integrate single-cell measurements not only across scRNA-seq technologies, but also across different modalities.
Journal ArticleDOI
Pathological findings of COVID-19 associated with acute respiratory distress syndrome.
Zhe Xu,Lei Shi,Yijin Wang,Ji-Yuan Zhang,Lei Huang,Chao Zhang,Shuhong Liu,Peng Zhao,Hongxia Liu,Li Zhu,Yanhong Tai,Changqing Bai,Tingting Gao,Jin-Wen Song,Peng Xia,Jing-Hui Dong,Jingmin Zhao,Fu-Sheng Wang +17 more
TL;DR: O surto do novo coronavÃrus (COVID-19) em Wuhan, China, iniciado em dezembro de 2019, evoluiu para se tornar uma pandemia global A.
Journal ArticleDOI
The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2
Alexander E. Gorbalenya,Susan C. Baker,Ralph S. Baric,Raoul J. de Groot,Christian Drosten,Anastasia A. Gulyaeva,Bart L. Haagmans,Chris Lauber,Andrey M. Leontovich,Benjamin W. Neuman,Dmitry Penzar,Stanley Perlman,Leo L.M. Poon,Dmitry V. Samborskiy,Igor A. Sidorov,Isabel Sola,John Ziebuhr +16 more
TL;DR: The independent zoonotic transmission of SARS-CoV and SARS -CoV-2 highlights the need for studying viruses at the species level to complement research focused on individual pathogenic viruses of immediate significance.
Related Papers (5)
A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.
David E. Gordon,Gwendolyn M. Jang,Mehdi Bouhaddou,Jiewei Xu,Kirsten Obernier,Kris M. White,Matthew J. O’Meara,Veronica V. Rezelj,Jeffrey Z. Guo,Danielle L. Swaney,Tia A. Tummino,Ruth Hüttenhain,Robyn M. Kaake,Alicia L. Richards,Beril Tutuncuoglu,Helene Foussard,Jyoti Batra,Kelsey M. Haas,Maya Modak,Minkyu Kim,Paige Haas,Benjamin J. Polacco,Hannes Braberg,Jacqueline M. Fabius,Manon Eckhardt,Margaret Soucheray,Melanie J. Bennett,Merve Cakir,Michael McGregor,Qiongyu Li,Bjoern Meyer,Ferdinand Roesch,Thomas Vallet,Alice Mac Kain,Lisa Miorin,Elena Moreno,Zun Zar Chi Naing,Yuan Zhou,Shiming Peng,Ying Shi,Ziyang Zhang,Wenqi Shen,Ilsa T Kirby,James E. Melnyk,John S. Chorba,Kevin Lou,Shizhong Dai,Inigo Barrio-Hernandez,Danish Memon,Claudia Hernandez-Armenta,Jiankun Lyu,Christopher J.P. Mathy,Tina Perica,Kala Bharath Pilla,Sai J. Ganesan,Daniel J. Saltzberg,Rakesh Ramachandran,Xi Liu,Sara Brin Rosenthal,Lorenzo Calviello,Srivats Venkataramanan,Jose Liboy-Lugo,Yizhu Lin,Xi Ping Huang,Yongfeng Liu,Stephanie A. Wankowicz,Markus Bohn,Maliheh Safari,Fatima S. Ugur,Cassandra Koh,Nastaran Sadat Savar,Quang Dinh Tran,Djoshkun Shengjuler,Sabrina J. Fletcher,Michael C. O’Neal,Yiming Cai,Jason C.J. Chang,David J. Broadhurst,Saker Klippsten,Phillip P. Sharp,Nicole A. Wenzell,Duygu Kuzuoğlu-Öztürk,Hao-Yuan Wang,Raphael Trenker,Janet M. Young,Devin A. Cavero,Devin A. Cavero,Joseph Hiatt,Joseph Hiatt,Theodore L. Roth,Ujjwal Rathore,Ujjwal Rathore,Advait Subramanian,Julia Noack,Mathieu Hubert,Robert M. Stroud,Alan D. Frankel,Oren S. Rosenberg,Kliment A. Verba,David A. Agard,Melanie Ott,Michael Emerman,Natalia Jura,Mark von Zastrow,Eric Verdin,Eric Verdin,Alan Ashworth,Olivier Schwartz,Christophe d'Enfert,Shaeri Mukherjee,Matthew P. Jacobson,Harmit S. Malik,Danica Galonić Fujimori,Trey Ideker,Charles S. Craik,Stephen N. Floor,James S. Fraser,John D. Gross,Andrej Sali,Bryan L. Roth,Davide Ruggero,Jack Taunton,Tanja Kortemme,Pedro Beltrao,Marco Vignuzzi,Adolfo García-Sastre,Kevan M. Shokat,Brian K. Shoichet,Nevan J. Krogan +128 more
Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients.
Jérôme Hadjadj,Nader Yatim,Laura Barnabei,Aurélien Corneau,Jeremy Boussier,Nikaïa Smith,Hélène Péré,Bruno Charbit,Vincent Bondet,Camille Chenevier-Gobeaux,Paul Breillat,Nicolas Carlier,Rémy Gauzit,Caroline Morbieu,Frédéric Pène,Nathalie Marin,Nicolas Roche,Tali Anne Szwebel,Sarah H. Merkling,Jean-Marc Treluyer,David Veyer,Luc Mouthon,Catherine Blanc,Pierre-Louis Tharaux,Flore Rozenberg,Alain Fischer,Alain Fischer,Alain Fischer,Darragh Duffy,Frédéric Rieux-Laucat,Solen Kernéis,Solen Kernéis,Benjamin Terrier +32 more
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Peng Zhou,Xing-Lou Yang,Xian Guang Wang,Ben Hu,Lei Zhang,Wei Zhang,Hao Rui Si,Yan Zhu,Bei Li,Chao Lin Huang,Hui-Dong Chen,Jing Chen,Yun Luo,Hua Guo,Ren Di Jiang,Meiqin Liu,Ying Chen,Xu Rui Shen,Xi Wang,Xiao Shuang Zheng,Kai Zhao,Quanjiao Chen,Fei Deng,Lin Lin Liu,Bing Yan,Fa Xian Zhan,Yan-Yi Wang,Gengfu Xiao,Zhengli Shi +28 more