Resurrection of 2'-5'-oligoadenylate synthetase 1 (OAS1) from the ancestor of modern horseshoe bats blocks SARS-CoV-2 replication.
Resurrection of 2'-5'-oligoadenylate synthetase 1 (OAS1) from the ancestor of modern horseshoe bats blocks SARS-CoV-2 replication.
复制标题
DOI：
10.1371/journal.pbio.3002398
复制
发表时间：
2023-11
期刊：
影响因子：
9.8
通讯作者：
中科院分区：
文献类型：
--
作者：
异戊二烯化形式的人2′-5′-寡腺苷酸合成酶1（OAS 1）蛋白已被证明可以有效抑制严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）的复制，该病毒是导致2019年冠状病毒病（COVID-19）大流行的病毒。然而，在马蹄蝙蝠（总科Rhinolophoidea），SARS相关的冠状病毒（SARSr冠状病毒）的水库主机，OAS 1的直系同源物，已经失去了这种抗病毒活性所需的异戊二烯化信号。在此，我们使用了一种祖先状态重建的方法来预测和重建在体外，最有可能的OAS 1蛋白序列表达的Rhinolophoidea共同祖先之前，其异戊二烯化损失（RhinoCA OAS 1）。我们在体外外源表达了古蝙蝠蛋白，以表明与其非异戊二烯化的马蹄蝙蝠后代不同，RhinoCA OAS 1成功地阻断了SARS-CoV-2的复制。使用蛋白质结构预测与进化假设检验方法相结合，我们突出了独特的多样化选择下的特定OAS 1的进化中的Rhinolophoidea网站。这些位点位于RNA结合区和异戊二烯化信号所在的蛋白质C末端附近。我们的研究结果证实，OAS 1异戊烯化损失在基地的Rhinolophoidea分支消融的能力，OAS 1限制SARSr冠状病毒复制，并在这些蝙蝠基因的后续进化可能有利于替代功能。这些发现可以促进我们对SARSr-CoV与马蹄蝠之间紧密联系的理解。人类OAS 1蛋白限制SARS-CoV-2复制，但马蹄蝙蝠OAS 1已经失去了这种能力。这项研究重建了所有马蹄蝙蝠祖先的6000万年前的功能性OAS 1蛋白，并揭示了这种古老的抗病毒机制是如何在蝙蝠中丢失的。
The prenylated form of the human 2′-5′-oligoadenylate synthetase 1 (OAS1) protein has been shown to potently inhibit the replication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic. However, the OAS1 orthologue in the horseshoe bats (superfamily Rhinolophoidea), the reservoir host of SARS-related coronaviruses (SARSr-CoVs), has lost the prenylation signal required for this antiviral activity. Herein, we used an ancestral state reconstruction approach to predict and reconstitute in vitro, the most likely OAS1 protein sequence expressed by the Rhinolophoidea common ancestor prior to its prenylation loss (RhinoCA OAS1). We exogenously expressed the ancient bat protein in vitro to show that, unlike its non-prenylated horseshoe bat descendants, RhinoCA OAS1 successfully blocks SARS-CoV-2 replication. Using protein structure predictions in combination with evolutionary hypothesis testing methods, we highlight sites under unique diversifying selection specific to OAS1’s evolution in the Rhinolophoidea. These sites are located near the RNA-binding region and the C-terminal end of the protein where the prenylation signal would have been. Our results confirm that OAS1 prenylation loss at the base of the Rhinolophoidea clade ablated the ability of OAS1 to restrict SARSr-CoV replication and that subsequent evolution of the gene in these bats likely favoured an alternative function. These findings can advance our understanding of the tightly linked association between SARSr-CoVs and horseshoe bats. The human OAS1 protein restricts SARS-CoV-2 replication, but the horseshoe bat OAS1 has lost this ability. This study reconstructs the functional 60-million-year-old OAS1 protein ancestral to all horseshoe bats, and reveals how this ancient antiviral mechanism was lost in the bats.
登录
查看更多内容
影响因子：
3.3
作者：
Mozzi A;Pontremoli C;Forni D;Clerici M;Pozzoli U;Bresolin N;Cagliani R;Sironi M
通讯作者：
Sironi M
影响因子：
6.4
作者：
Gusho E;Zhang R;Jha BK;Thornbrough JM;Dong B;Gaughan C;Elliott R;Weiss SR;Silverman RH
通讯作者：
Silverman RH
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
DOI：
10.1038/nri3719
发表时间：
2014-08
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Hornung V;Hartmann R;Ablasser A;Hopfner KP
通讯作者：
Hopfner KP
影响因子：
10.7
作者：
Nguyen LT;Schmidt HA;von Haeseler A;Minh BQ
通讯作者：
Minh BQ