Coronaviruses are able to establish persistence. However, how coronaviruses react to persistence and whether the selected viruses have altered their characteristics remain unclear. In this study, we found that the persistent infection of bovine coronavirus (BCoV), which is in the same genus as SARS-COV-2, led to alterations of genome structure, attenuation of gene expression, and the synthesis of subgenomic mRNA (sgmRNA) with a previously unidentified pattern. Subsequent analyses revealed that the altered genome structures were associated with the attenuation of gene expression. In addition, the genome structure at the 5′ terminus and the cellular environment during the persistence were responsible for the sgmRNA synthesis, solving the previously unanswered question regarding the selection of transcription regulatory sequence for synthesis of BCoV sgmRNA 12.7. Although the BCoV variants (BCoV-p95) selected under the persistence replicated efficiently in cells without persistent infection, its pathogenicity was still lower than that of wild-type (wt) BCoV. Furthermore, in comparison with wt BCoV, the variant BCoV-p95 was not able to efficiently adapt to the challenges of alternative environments, suggesting wt BCoV is genetically robust. We anticipate that the findings derived from this fundamental research can contribute to the disease control and treatments against coronavirus infection including SARS-CoV-2.

中文翻译：

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冠状病毒持久性对基因组结构及后续基因表达、致病性和适应能力的影响


冠状病毒能够建立持久性。然而，冠状病毒如何对持久性做出反应以及所选病毒是否改变了其特征仍不清楚。在本研究中，我们发现与SARS-COV-2同属的牛冠状病毒（BCoV）的持续感染导致基因组结构改变、基因表达减弱以及亚基因组mRNA（sgmRNA）的合成。 ）具有先前未识别的模式。随后的分析表明，基因组结构的改变与基因表达的减弱有关。此外，5'末端的基因组结构和持续期间的细胞环境负责sgmRNA的合成，解决了之前关于选择合成BCoV sgmRNA 12.7的转录调控序列的问题。尽管在持久性下选择的BCoV变种（BCoV-p95）在没有持续感染的细胞中有效复制，但其致病性仍然低于野生型（wt）BCoV。此外，与野生型 BCoV 相比，变异型 BCoV-p95 无法有效适应替代环境的挑战，这表明野生型 BCoV 在遗传上具有稳健性。我们预计这项基础研究的结果可以有助于疾病控制和治疗包括 SARS-CoV-2 在内的冠状病毒感染。