The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a great threat to human health. The interplay between the virus and host plays a crucial role in successful virus replication and transmission. Understanding host–virus interactions are essential for the development of new COVID-19 treatment strategies. Here, we show that SARS-CoV-2 infection triggers redistribution of cyclin D1 and cyclin D3 from the nucleus to the cytoplasm, followed by proteasomal degradation. No changes to other cyclins or cyclin-dependent kinases were observed. Further, cyclin D depletion was independent of SARS-CoV-2-mediated cell cycle arrest in the early S phase or S/G2/M phase. Cyclin D3 knockdown by small-interfering RNA specifically enhanced progeny virus titres in supernatants. Finally, cyclin D3 co-immunoprecipitated with SARS-CoV-2 envelope (E) and membrane (M) proteins. We propose that cyclin D3 impairs the efficient incorporation of envelope protein into virions during assembly and is depleted during SARS-CoV-2 infection to restore efficient assembly and release of newly produced virions.

中文翻译：

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Cyclin D3 限制 SARS-CoV-2 包膜掺入病毒粒子并干扰病毒传播


由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的COVID-19大流行对人类健康构成巨大威胁。病毒和宿主之间的相互作用对于病毒的成功复制和传播起着至关重要的作用。了解宿主与病毒的相互作用对于制定新的 COVID-19 治疗策略至关重要。在这里，我们发现 SARS-CoV-2 感染触发细胞周期蛋白 D1 和细胞周期蛋白 D3 从细胞核重新分布到细胞质，然后发生蛋白酶体降解。没有观察到其他细胞周期蛋白或细胞周期蛋白依赖性激酶的变化。此外，细胞周期蛋白 D 的消耗与 SARS-CoV-2 介导的早期 S 期或 S/G2/M 期细胞周期停滞无关。通过小干扰 RNA 敲低细胞周期蛋白 D3 可特异性增强上清液中的子代病毒滴度。最后，细胞周期蛋白 D3 与 SARS-CoV-2 包膜 (E) 和膜 (M) 蛋白进行免疫共沉淀。我们认为，细胞周期蛋白 D3 在组装过程中会损害包膜蛋白有效掺入病毒粒子，并在 SARS-CoV-2 感染期间被耗尽，以恢复新产生的病毒粒子的有效组装和释放。