Recurrent viral capture of cellular phosphodiesterases that antagonize OAS-RNase L.
Recurrent viral capture of cellular phosphodiesterases that antagonize OAS-RNase L.
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拮抗OAS-RNase L的细胞磷酸二酯酶的反复病毒捕获。
DOI：
10.1073/pnas.2312691121
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发表时间：
2024-01-30
影响因子：
11.1
通讯作者：
Elde, Nels C.
中科院分区：
文献类型：
--
作者：
Goldstein, Stephen A.;Elde, Nels C.
宿主基因向病毒基因组的水平基因转移（HGT）是RNA病毒进化的一种常见但未被充分认识的方式。我们使用序列比较和蛋白质结构预测的组合来重建病毒磷酸二酯酶（PDE）基因的进化历史。由巢状病毒和轮状病毒编码的PDE似乎是从宿主AKAP7样PDE基因传下来的，并且是抗病毒OAS-RNase L途径的有效拮抗剂。通过描述这些基因的进化历史，我们揭示了HGT如何塑造病毒与宿主免疫力的相互作用。通过整合进化方法，我们克服了病毒和细胞PDE多样性之间巨大的序列差异所带来的挑战，表明细胞AKAP7样PDE被两个RNA病毒家族反复获得。病毒编码的磷酸二酯酶（PDE）是通过细胞PDE祖先基因的水平转移而获得的。病毒PDE抑制OAS-RNase L抗病毒途径，这是先天免疫应答的关键效应子组分。虽然这些蛋白质的功能已经得到了很好的表征，但这些基因获得的起源却不太清楚。系统发育分析显示，至少有五个独立的PDE收购事件的祖先病毒。我们发现了PDE编码基因在不同属的冠状病毒之间水平转移的证据。巢状病毒目中的三个病毒进化枝：merbecoviruses（MERS-CoV）、embecoviruses（HCoV-OC 43）和toroviruses编码独立获得的PDE，啮齿动物冠状病毒的进化枝通过最近的水平转移获得embecovirus PDE。在轮状病毒中，轮状病毒A的PDE独立于共享共同祖先的轮状病毒B和G PDE获得。保守的基序分析表明，所有病毒PDE和哺乳动物AKAP7蛋白之间的相似祖先的联系，尽管低水平的序列保守性。此外，我们使用祖先序列重建和结构建模来揭示这些蛋白质之间的序列和结构差异并不相关。具体地，梅尔贝科病毒PDE与祖先蛋白和人AKAP 7 PDE的解析结构在结构上是不同的，因为它们彼此不同。相比之下，轮状病毒B和G PDE的比较显示，尽管有证据表明其中一个功能丧失，但结构几乎没有变化，这表明保守催化位点之外的影响性变化。这些发现凸显了病毒偏微分方程复杂且不稳定的进化历史，并为促进未来的研究提供了框架。
Horizontal gene transfer (HGT) of host genes to virus genomes is a common but underappreciated means of RNA virus evolution. We used a combination of sequence comparisons and protein structure predictions to reconstruct the evolutionary history of viral phosphodiesterase (PDE) genes. PDEs encoded by nidoviruses and rotaviruses appear to be descended from host AKAP7-like PDE genes and are potent antagonists of the antiviral OAS-RNase L pathway. By characterizing the evolutionary history of these genes, we shed light on how HGT shaped virus interactions with host immunity. By integrating evolutionary approaches, we overcome challenges posed by vast sequence divergence across viral and cellular PDE diversity to show that cellular AKAP7-like PDEs were recurrently acquired by two families of RNA viruses. Phosphodiesterases (PDEs) encoded by viruses are putatively acquired by horizontal transfer of cellular PDE ancestor genes. Viral PDEs inhibit the OAS-RNase L antiviral pathway, a key effector component of the innate immune response. Although the function of these proteins is well-characterized, the origins of these gene acquisitions are less clear. Phylogenetic analysis revealed at least five independent PDE acquisition events by ancestral viruses. We found evidence that PDE-encoding genes were horizontally transferred between coronaviruses belonging to different genera. Three clades of viruses within Nidovirales: merbecoviruses (MERS-CoV), embecoviruses (HCoV-OC43), and toroviruses encode independently acquired PDEs, and a clade of rodent alphacoronaviruses acquired an embecovirus PDE via recent horizontal transfer. Among rotaviruses, the PDE of rotavirus A was acquired independently from rotavirus B and G PDEs, which share a common ancestor. Conserved motif analysis suggests a link between all viral PDEs and a similar ancestor among the mammalian AKAP7 proteins despite low levels of sequence conservation. Additionally, we used ancestral sequence reconstruction and structural modeling to reveal that sequence and structural divergence are not well-correlated among these proteins. Specifically, merbecovirus PDEs are as structurally divergent from the ancestral protein and the solved structure of human AKAP7 PDE as they are from each other. In contrast, comparisons of rotavirus B and G PDEs reveal virtually unchanged structures despite evidence for loss of function in one, suggesting impactful changes that lie outside conserved catalytic sites. These findings highlight the complex and volatile evolutionary history of viral PDEs and provide a framework to facilitate future studies.
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影响因子：
2.9
作者：
Brandmann T;Jinek M
通讯作者：
Jinek M
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
影响因子：
4.9
作者：
Forni, Diego;Cagliani, Rachele;Molteni, Cristian;Arrigoni, Federica;Mozzi, Alessandra;Clerici, Mario;De Gioia, Luca;Sironi, Manuela
通讯作者：
Sironi, Manuela
DOI：
10.1073/pnas.1519657113
发表时间：
2016-02-23
影响因子：
11.1
作者：
Li, Yize;Banerjee, Shuvojit;Weiss, Susan R.
通讯作者：
Weiss, Susan R.
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