Distinct evolutionary trajectories of SARS-CoV-2-interacting proteins in bats and primates identify important host determinants of COVID-19.
Distinct evolutionary trajectories of SARS-CoV-2-interacting proteins in bats and primates identify important host determinants of COVID-19.
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DOI：
10.1073/pnas.2206610119
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发表时间：
2022-08-30
影响因子：
11.1
通讯作者：
Etienne, Lucie
中科院分区：
文献类型：
--
作者：
Cariou, Marie;Picard, Lea;Gueguen, Laurent;Jacquet, Stephanie;Cimarelli, Andrea;Fregoso, Oliver, I;Molaro, Antoine;Navratil, Vincent;Etienne, Lucie
关键词：
冠状病毒病19（COVID-19）大流行是由严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）引起的，这是一种从蝙蝠水库溢出的冠状病毒。然而，驱动SARS-CoV-2易感性和COVID-19严重性的宿主遗传决定因素在很大程度上是未知的。了解与SARS-CoV-2相互作用的细胞蛋白如何在灵长类动物和蝙蝠中进化，对于破译人类和蝙蝠中病毒宿主之间感染结果的差异至关重要。在这里，我们对数百种SARS-CoV-2相互作用蛋白进行了比较功能遗传分析，以研究数百万年来病毒-宿主界面的适应性，指出基因相似或差异参与进化军备竞赛，这可能是体内致病差异的基础。冠状病毒病19（COVID-19）大流行是由严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）引起的，这是一种从蝙蝠水库溢出的冠状病毒。尽管有许多临床试验和疫苗，但负担仍然巨大，SARS-CoV-2易感性和COVID-19严重程度的宿主决定因素在很大程度上仍然未知。在灵长类动物和蝙蝠基因组中通过比较功能遗传分析检测到的正选择的签名可以揭示发生在病毒-宿主界面的重要和特定的适应。我们对334个SARS-CoV-2相互作用蛋白进行了高通量进化分析，以确定SARS-CoV适应性位点，并揭示现代人类，灵长类动物和蝙蝠之间的功能差异。利用DGINN（检测遗传创新），我们确定了38蝙蝠和81灵长类动物蛋白的正选择标记。包括ACE 2受体在内的17个基因在两种哺乳动物中都存在适应性标记，表明共同的病毒-宿主界面和过去流行的冠状病毒塑造了它们的基因组。然而，84个基因在蝙蝠和灵长类动物中表现出不同的适应性。值得注意的是，参与炎症RIPK 1的泛素化和磷酸化的残基在蝙蝠中迅速进化，而不是灵长类动物，这表明与人类不同的炎症调节。此外，我们在灵长类动物中发现了具有典型病毒-宿主军备竞赛标记的残基，例如在进入因子TMPRSS 2或自噬适配器FYCO 1中，指向可能是药物靶点的宿主特异性体内界面。最后，我们发现灵长类动物中适应的FYCO 1位点与严重的COVID-19相关，支持它们在发病机制和复制中的重要性。总的来说，我们确定了蝙蝠和灵长类动物中涉及SARS-CoV-2感染的适应性，启发了病毒易感性和严重性的现代遗传决定因素。
The coronavirus disease 19 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a coronavirus that spilled over from the bat reservoir. However, the host genetic determinants that drive SARS-CoV-2 susceptibility and COVID-19 severity are largely unknown. Understanding how cellular proteins interacting with SARS-CoV-2 have evolved in primates and bats is of primary importance to decipher differences in the infection outcome between humans and the viral reservoir in bats. Here, we performed comparative functional genetic analyses of hundreds of SARS-CoV-2-interacting proteins to study virus–host interface adaptation over millions of years, pointing to genes similarly—or differentially—engaged in evolutionary arms races and that may be at the basis of in vivo pathogenic differences. The coronavirus disease 19 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a coronavirus that spilled over from the bat reservoir. Despite numerous clinical trials and vaccines, the burden remains immense, and the host determinants of SARS-CoV-2 susceptibility and COVID-19 severity remain largely unknown. Signatures of positive selection detected by comparative functional genetic analyses in primate and bat genomes can uncover important and specific adaptations that occurred at virus–host interfaces. We performed high-throughput evolutionary analyses of 334 SARS-CoV-2-interacting proteins to identify SARS-CoV adaptive loci and uncover functional differences between modern humans, primates, and bats. Using DGINN (Detection of Genetic INNovation), we identified 38 bat and 81 primate proteins with marks of positive selection. Seventeen genes, including the ACE2 receptor, present adaptive marks in both mammalian orders, suggesting common virus–host interfaces and past epidemics of coronaviruses shaping their genomes. Yet, 84 genes presented distinct adaptations in bats and primates. Notably, residues involved in ubiquitination and phosphorylation of the inflammatory RIPK1 have rapidly evolved in bats but not primates, suggesting different inflammation regulation versus humans. Furthermore, we discovered residues with typical virus–host arms race marks in primates, such as in the entry factor TMPRSS2 or the autophagy adaptor FYCO1, pointing to host-specific in vivo interfaces that may be drug targets. Finally, we found that FYCO1 sites under adaptation in primates are those associated with severe COVID-19, supporting their importance in pathogenesis and replication. Overall, we identified adaptations involved in SARS-CoV-2 infection in bats and primates, enlightening modern genetic determinants of virus susceptibility and severity.
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DOI：
10.1038/s41577-021-00633-9
发表时间：
2022-08
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Crow YJ;Stetson DB
通讯作者：
Stetson DB
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
FYCO1 和 MAP1LC3A 相互作用的结构基础揭示了 Atg8 家族蛋白的新型结合模式。
影响因子：
13.3
作者：
Cheng, Xiaofang;Wang, Yingli;Pan, Lifeng
通讯作者：
Pan, Lifeng
影响因子：
30.3
作者：
Boys IN;Xu E;Mar KB;De La Cruz-Rivera PC;Eitson JL;Moon B;Schoggins JW
通讯作者：
Schoggins JW
影响因子：
6.7
作者：
Fregoso OI;Ahn J;Wang C;Mehrens J;Skowronski J;Emerman M
通讯作者：
Emerman M