The Functional Classification of ORF8 in SARS-CoV-2 Replication, Immune Evasion, and Viral Pathogenesis Inferred through Phylogenetic Profiling.
The Functional Classification of ORF8 in SARS-CoV-2 Replication, Immune Evasion, and Viral Pathogenesis Inferred through Phylogenetic Profiling.
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ORF 8在SARS-CoV-2复制、免疫逃避和通过系统发育分析推断的病毒发病机制中的功能分类。
DOI：
10.1177/11769343211003079
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Ito M
中科院分区：
文献类型：
--
作者：
Fahmi M;Kitagawa H;Yasui G;Kubota Y;Ito M
ORF8是SARS-CoV-2的一个高度变异的基因组区域。尽管非必需和精确的功能尚不清楚，但已有研究表明，该蛋白有助于SARS-CoV-2在早期分泌途径中的复制和免疫逃避。我们利用人HEK293T细胞中SARS-CoV-2蛋白的结合伙伴，并在446个真核物种中进行全基因组系统发育分析和聚类分析，以预测和发现基于共同进化的共享相关功能机制的ORF8结合伙伴。结果将47个ORF8结合蛋白分为3组(第1~3组)，分别在脊椎动物(第1组)、后生动物(第2组)和真核生物(第3组)中保守。基因本体论分析表明，组1没有明显的相关生物学过程，而组2和组3分别与糖蛋白生物合成过程和泛素依赖内质网相关的降解途径有关。总体而言，我们的结果对可能与SARS-CoV-2病毒发病相关的潜在基因进行了分类，特别是与急性呼吸窘迫综合征和分泌途径相关。在这里，我们讨论了ORF8在病毒致病机制中的可能作用，以及通过分泌途径辅助病毒复制和免疫逃避的可能作用，以及与ORF8快速进化相关的可能因素。
ORF8 is a highly variable genomic region of SARS-CoV-2. Although non-essential and the precise functions are unknown, it has been suggested that this protein assists in SARS-CoV-2 replication in the early secretory pathway and in immune evasion. We utilized the binding partners of SARS-CoV-2 proteins in human HEK293T cells and performed genome-wide phylogenetic profiling and clustering analyses in 446 eukaryotic species to predict and discover ORF8 binding partners that share associated functional mechanisms based on co-evolution. Results classified 47 ORF8 binding partner proteins into 3 clusters (groups 1-3), which were conserved in vertebrates (group 1), metazoan (group 2), and eukaryotes (group 3). Gene ontology analysis indicated that group 1 had no significant associated biological processes, while groups 2 and 3 were associated with glycoprotein biosynthesis process and ubiquitin-dependent endoplasmic reticulum-associated degradation pathways, respectively. Collectively, our results classified potential genes that might be associated with SARS-CoV-2 viral pathogenesis, specifically related to acute respiratory distress syndrome, and the secretory pathway. Here, we discuss the possible role of ORF8 in viral pathogenesis and in assisting viral replication and immune evasion via secretory pathway, as well as the possible factors associated with the rapid evolution of ORF8.
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影响因子：
5.6
作者：
Nakamura, Takahiro;Fahmi, Muhamad;Ito, Masahiro
通讯作者：
Ito, Masahiro
影响因子：
5.8
作者：
Braun, Maya;Sharon, Elad;Tabach, Yuval
通讯作者：
Tabach, Yuval
影响因子：
12.3
作者：
Kelwick R;Desanlis I;Wheeler GN;Edwards DR
通讯作者：
Edwards DR
影响因子：
10.7
作者：
Baalsrud HT;Tørresen OK;Solbakken MH;Salzburger W;Hanel R;Jakobsen KS;Jentoft S
通讯作者：
Jentoft S
影响因子：
4.6
作者：
Muth D;Corman VM;Roth H;Binger T;Dijkman R;Gottula LT;Gloza-Rausch F;Balboni A;Battilani M;Rihtarič D;Toplak I;Ameneiros RS;Pfeifer A;Thiel V;Drexler JF;Müller MA;Drosten C
通讯作者：
Drosten C