Decreased inhibition of exosomal miRNAs on SARS-CoV-2 replication underlies poor outcomes in elderly people and diabetic patients.
Decreased inhibition of exosomal miRNAs on SARS-CoV-2 replication underlies poor outcomes in elderly people and diabetic patients.
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DOI：
10.1038/s41392-021-00716-y
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发表时间：
2021-08-11
影响因子：
39.3
通讯作者：
Zhang CY
中科院分区：
文献类型：
--
作者：
Wang Y;Zhu X;Jiang XM;Guo J;Fu Z;Zhou Z;Yang P;Guo H;Guo X;Liang G;Zeng P;Xiao G;Ma J;Yin X;Zhang LK;Yan C;Zhang CY
老年人和合并症患者感染COVID-19的风险更高，导致严重的并发症和高死亡率。然而，其潜在机制尚不清楚。在这项研究中，我们研究了血清外泌体中的miRNA是否可以发挥抗病毒功能，并影响老年人和糖尿病患者对COVID-19的反应。首先，我们通过高通量测序和定量实时PCR分析鉴定了四种miRNA（miR-7- 5 p，miR-24- 3 p，miR-145- 5 p和miR-223- 3 p），它们在老年人和糖尿病组中显著减少。我们进一步证明，这些miRNAs，无论是在exosome或以游离形式，可以直接抑制S蛋白的表达和SARS-CoV-2复制。年轻人血清exosomes可抑制SARS-CoV-2复制和S蛋白表达，而老年人和糖尿病患者血清exosomes的抑制作用明显减弱。此外，在健康志愿者的血清中，四种循环miRNA中的三种在8周的连续体育锻炼后显著增加。从这些志愿者中分离的血清外泌体也显示出对S蛋白表达和SARS-CoV-2复制的较强抑制作用。我们的研究首次证明，循环外泌体miRNA可以直接抑制SARS-CoV-2复制，并可能为年轻人和老年人或合并症患者对COVID-19的反应差异提供可能的解释。
Elderly people and patients with comorbidities are at higher risk of COVID-19 infection, resulting in severe complications and high mortality. However, the underlying mechanisms are unclear. In this study, we investigate whether miRNAs in serum exosomes can exert antiviral functions and affect the response to COVID-19 in the elderly and people with diabetes. First, we identified four miRNAs (miR-7-5p, miR-24-3p, miR-145-5p and miR-223-3p) through high-throughput sequencing and quantitative real-time PCR analysis, that are remarkably decreased in the elderly and diabetic groups. We further demonstrated that these miRNAs, either in the exosome or in the free form, can directly inhibit S protein expression and SARS-CoV-2 replication. Serum exosomes from young people can inhibit SARS-CoV-2 replication and S protein expression, while the inhibitory effect is markedly decreased in the elderly and diabetic patients. Moreover, three out of the four circulating miRNAs are significantly increased in the serum of healthy volunteers after 8-weeks’ continuous physical exercise. Serum exosomes isolated from these volunteers also showed stronger inhibitory effects on S protein expression and SARS-CoV-2 replication. Our study demonstrates for the first time that circulating exosomal miRNAs can directly inhibit SARS-CoV-2 replication and may provide a possible explanation for the difference in response to COVID-19 between young people and the elderly or people with comorbidities.
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影响因子：
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