Identification of DAXX as a restriction factor of SARS-CoV-2 through a CRISPR/Cas9 screen.
Identification of DAXX as a restriction factor of SARS-CoV-2 through a CRISPR/Cas9 screen.
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通过CRISPR/Cas9筛选将DAXX鉴定为SARS-CoV-2的限制因子。
DOI：
10.1038/s41467-022-30134-9
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发表时间：
2022-05-04
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
在细胞培养中，干扰素限制SARS-CoV-2的复制，但只有少数干扰素刺激的基因具有抗SARS-CoV-2的抗病毒活性。在这里，我们描述了一种功能性CRISPR/Cas9筛选，旨在识别SARS-CoV-2限制因子。我们鉴定了DAXX，一种存在于PML核小体中的支架蛋白，已知其限制DNA病毒和逆转录病毒的复制，作为SARS-CoV-2和SARS-CoV在人类细胞中复制的有效抑制剂。DAXX的基础表达足以限制SARS-CoV-2的复制，DAXX的过表达进一步限制了感染。DAXX限制了SARS-CoV-2生命周期的早期进入后步骤。DAXX介导的SARS-CoV-2的限制作用不依赖于SUMO化途径，但依赖于其D/E结构域，这也是其蛋白折叠活性所必需的。SARS-CoV-2感染触发DAXX重新定位到细胞质位点并促进其降解。从机制上讲，这一过程是由病毒木瓜蛋白酶样蛋白酶（PLpro）和蛋白酶体介导的。总之，这些结果表明DAXX限制SARS-CoV-2，这反过来又进化出一种抵消其作用的机制。在这里，Mac Kain和Maarifi等人进行了功能性CRISPR/Cas9筛选，以鉴定A549细胞中的SARS-CoV-2限制因子。他们鉴定了DAXX，一种具有不同功能的核体支架蛋白，在SARS-CoV-2进入后具有抗病毒活性，而SARS-CoV-2已经进化出一种通过PLpro介导的蛋白酶体降解来抵消其作用的机制。
Interferon restricts SARS-CoV-2 replication in cell culture, but only a handful of Interferon Stimulated Genes with antiviral activity against SARS-CoV-2 have been identified. Here, we describe a functional CRISPR/Cas9 screen aiming at identifying SARS-CoV-2 restriction factors. We identify DAXX, a scaffold protein residing in PML nuclear bodies known to limit the replication of DNA viruses and retroviruses, as a potent inhibitor of SARS-CoV-2 and SARS-CoV replication in human cells. Basal expression of DAXX is sufficient to limit the replication of SARS-CoV-2, and DAXX over-expression further restricts infection. DAXX restricts an early, post-entry step of the SARS-CoV-2 life cycle. DAXX-mediated restriction of SARS-CoV-2 is independent of the SUMOylation pathway but dependent on its D/E domain, also necessary for its protein-folding activity. SARS-CoV-2 infection triggers the re-localization of DAXX to cytoplasmic sites and promotes its degradation. Mechanistically, this process is mediated by the viral papain-like protease (PLpro) and the proteasome. Together, these results demonstrate that DAXX restricts SARS-CoV-2, which in turn has evolved a mechanism to counteract its action. Here, Mac Kain and Maarifi et al. perform a functional CRISPR/Cas9 screen to identify SARS-CoV-2 restriction factors in A549 cells. They identify DAXX, a scaffold protein of nuclear bodies with diverse functions, that has anti-viral activity post SARS-CoV-2 entry, while SARS-CoV-2 has evolved a mechanism to counteract its action via PLpro-mediated proteasomal degradation.
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影响因子：
3.8
作者：
Hoffmann, Markus;Wu, Yuan-Ju;Zimmer, Gert
通讯作者：
Zimmer, Gert
危及生命的Covid-19患者中针对I型IFN的自身抗体。
DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bastard P;Rosen LB;Zhang Q;Michailidis E;Hoffmann HH;Zhang Y;Dorgham K;Philippot Q;Rosain J;Béziat V;Manry J;Shaw E;Haljasmägi L;Peterson P;Lorenzo L;Bizien L;Trouillet-Assant S;Dobbs K;de Jesus AA;Belot A;Kallaste A;Catherinot E;Tandjaoui-Lambiotte Y;Le Pen J;Kerner G;Bigio B;Seeleuthner Y;Yang R;Bolze A;Spaan AN;Delmonte OM;Abers MS;Aiuti A;Casari G;Lampasona V;Piemonti L;Ciceri F;Bilguvar K;Lifton RP;Vasse M;Smadja DM;Migaud M;Hadjadj J;Terrier B;Duffy D;Quintana-Murci L;van de Beek D;Roussel L;Vinh DC;Tangye SG;Haerynck F;Dalmau D;Martinez-Picado J;Brodin P;Nussenzweig MC;Boisson-Dupuis S;Rodríguez-Gallego C;Vogt G;Mogensen TH;Oler AJ;Gu J;Burbelo PD;Cohen JI;Biondi A;Bettini LR;D'Angio M;Bonfanti P;Rossignol P;Mayaux J;Rieux-Laucat F;Husebye ES;Fusco F;Ursini MV;Imberti L;Sottini A;Paghera S;Quiros-Roldan E;Rossi C;Castagnoli R;Montagna D;Licari A;Marseglia GL;Duval X;Ghosn J;HGID Lab;NIAID-USUHS Immune Response to COVID Group;COVID Clinicians;COVID-STORM Clinicians;Imagine COVID Group;French COVID Cohort Study Group;Milieu Intérieur Consortium;CoV-Contact Cohort;Amsterdam UMC Covid-19 Biobank;COVID Human Genetic Effort;Tsang JS;Goldbach-Mansky R;Kisand K;Lionakis MS;Puel A;Zhang SY;Holland SM;Gorochov G;Jouanguy E;Rice CM;Cobat A;Notarangelo LD;Abel L;Su HC;Casanova JL
通讯作者：
Casanova JL
影响因子：
64.5
作者：
Daniloski Z;Jordan TX;Wessels HH;Hoagland DA;Kasela S;Legut M;Maniatis S;Mimitou EP;Lu L;Geller E;Danziger O;Rosenberg BR;Phatnani H;Smibert P;Lappalainen T;tenOever BR;Sanjana NE
通讯作者：
Sanjana NE
DOI：
10.1016/s0140-6736(13)60982-4
发表时间：
2013-06-29
期刊：
Lancet (London, England)
影响因子：
--
作者：
Guery B;Poissy J;el Mansouf L;Séjourné C;Ettahar N;Lemaire X;Vuotto F;Goffard A;Behillil S;Enouf V;Caro V;Mailles A;Che D;Manuguerra JC;Mathieu D;Fontanet A;van der Werf S;MERS-CoV study group
通讯作者：
MERS-CoV study group
DOI：
10.1074/jbc.ac120.013788
发表时间：
2020-10-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Felgenhauer U;Schoen A;Gad HH;Hartmann R;Schaubmar AR;Failing K;Drosten C;Weber F
通讯作者：
Weber F