Departamento de Ciências da Vida, Universidade de Coimbra. Calçada Martim de Freitas, 3000-456 Coimbra, Portugal; IDENTIFICA, Science and Technology Park of the University of Porto - UPTEC, Rua Alfredo Allen, N.°455/461, 4200-135 Porto, Portugal..
Infect Genet Evol. 2020 Nov;85:104525. doi: 10.1016/j.meegid.2020.104525. Epub 2020 Sep 2.
The new SARS-CoV-2 poses a significant threat to human health but many aspects of its basic biology remain unknown. Its genome encodes accessory genes that differ significantly within coronaviruses and contribute to the virus pathogenicity. Among accessory genes, open reading frame 8 (ORF8) stands out by being highly variable and showing structural changes suspected to be related with the virus ability to spread. However, the function of ORF8 remains to be elucidated, making it less studied than other SARS-CoV-2 genes. Here I show that ORF8 is poorly conserved among related coronaviruses. The ORF8 phylogeny built using 11,113 SARS-CoV-2 sequences revealed traces of a typical expanding population with a small number of highly frequent lineages. Interestingly, I detected several nonsense mutations and three main deletions in the ORF8 gene that either remove or significantly change the ORF8 protein. These findings suggest that SARS-CoV-2 can persist without a functional ORF8 protein. Deletion breakpoints were found located in predicted hairpins suggesting a possible involvement of these elements in the rearrangement process. Although the function of ORF8 remains to be elucidated, its structural plasticity and high diversity suggest an important role in SARS-CoV-2 pathogenicity.
新型严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）对人类健康构成重大威胁，但它的许多基本生物学特性仍不清楚。其基因组编码的辅助基因在冠状病毒中差异很大，有助于病毒的致病性。在辅助基因中，开放阅读框 8（ORF8）因其高度可变和显示出结构变化而引人注目，这些结构变化疑似与病毒的传播能力有关。然而，ORF8 的功能仍有待阐明，因此它的研究不如其他 SARS-CoV-2 基因多。在这里，我表明 ORF8 在相关冠状病毒中缺乏保守性。使用 11113 个 SARS-CoV-2 序列构建的 ORF8 系统发育树揭示了一个典型的扩张种群的痕迹，其中只有少数高度频繁的谱系。有趣的是，我在 ORF8 基因中检测到几个无意义突变和三个主要缺失，这些缺失要么消除要么显著改变 ORF8 蛋白。这些发现表明，SARS-CoV-2 可以在没有功能性 ORF8 蛋白的情况下持续存在。缺失断点位于预测的发夹结构中，这表明这些元件可能参与了重排过程。尽管 ORF8 的功能仍有待阐明，但它的结构可塑性和高度多样性表明它在 SARS-CoV-2 致病性中具有重要作用。
