ORF8 protein of SARS‐CoV‐2 reduces male fertility in mice
ORF8 protein of SARS‐CoV‐2 reduces male fertility in mice
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SARS-CoV-2 的 ORF8 蛋白降低小鼠雄性生育能力
DOI：
10.1002/jmv.27855
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发表时间：
2022-05
影响因子：
12.7
通讯作者：
Ji-An Pan
中科院分区：
文献类型：
--
作者：
Ting Yu;Qiao Ling;Mengxin Xu;Niu Wang;Lixia Wang;Hanwen Lin;Manqi Cao;Yong Ma;Yuanyuan Wang;Kuibiao Li;Du Liubing;Yunyun Jin;Ying Li;Deyin Guo;Xiaoxue Peng;Yao-Qing Chen;Bo Zhao;Ji-An Pan
开放阅读框（ORF 8）作为乙型冠状病毒属中进化最快的蛋白之一，其在体内的功能和潜在的病理后果尚不清楚。在这项研究中，我们表明ORF 8的分泌依赖于其N末端信号肽序列，并且可以被培养细胞中的活性氧清除剂和内质网-高尔基体转运抑制剂抑制。为了追踪其可能在体内分泌的影响，我们检查了2019冠状病毒病（COVID-19）康复患者的血浆样本，发现40至60岁的患者的抗体滴度高于40岁以下的患者。为了探索ORF 8的体内功能，我们通过尾静脉注射向小鼠施用ORF 8以模拟患者中的循环ORF 8。尽管在溶媒和ORF 8处理的小鼠之间未检测到体重、摄食量和活力的明显差异，但后者显示睾丸和附睾的形态异常，如5周龄雄性小鼠中中央导管腔丧失伴生育力降低所示。此外，对载体和ORF 8处理的小鼠之间睾丸中基因表达的分析确定了Col 1a 1表达的降低，已知Col 1a 1的丧失与小鼠的不育有关。虽然我们在小鼠中的观察结果是否可以转化为人类尚不清楚，但我们的研究提供了一种潜在的小鼠模型，可用于研究严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染对人类生殖系统的影响。
As one of the most rapidly evolving proteins of the genus Betacoronavirus, open reading frames (ORF8's) function and potential pathological consequence in vivo are still obscure. In this study, we show that the secretion of ORF8 is dependent on its N-terminal signal peptide sequence and can be inhibited by reactive oxygen species scavenger and endoplasmic reticulum-Golgi transportation inhibitor in cultured cells. To trace the effect of its possible in vivo secretion, we examined the plasma samples of coronavirus disease 2019 (COVID-19) convalescent patients and found that the patients aged from 40 to 60 had higher antibody titers than those under 40. To explore ORF8's in vivo function, we administered the mice with ORF8 via tail-vein injection to simulate the circulating ORF8 in the patient. Although no apparent difference in body weight, food intake, and vitality was detected between vehicle- and ORF8-treated mice, the latter displayed morphological abnormalities of testes and epididymides, as indicated by the loss of the central ductal lumen accompanied by a decreased fertility in 5-week-old male mice. Furthermore, the analysis of gene expression in the testes between vehicle- and ORF8-treated mice identified a decreased expression of Col1a1, the loss of which is known to be associated with mice's infertility. Although whether our observation in mice could be translated to humans remains unclear, our study provides a potential mouse model that can be used to investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the human reproductive system.
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影响因子：
5
作者：
Rashid F;Dzakah EE;Wang H;Tang S
通讯作者：
Tang S
影响因子：
16
作者：
Pan JA;Sun Y;Jiang YP;Bott AJ;Jaber N;Dou Z;Yang B;Chen JS;Catanzaro JM;Du C;Ding WX;Diaz-Meco MT;Moscat J;Ozato K;Lin RZ;Zong WX
通讯作者：
Zong WX
影响因子：
5.2
作者：
He Y;Wang J;Ren J;Zhao Y;Chen J;Chen X
通讯作者：
Chen X
DOI：
10.1016/j.bbrc.2021.02.080
发表时间：
2021-04-23
影响因子：
3.1
作者：
Pereira F
通讯作者：
Pereira F
通过libla-seq在康复covid-19患者中的SARS-COV-2特异性记忆B细胞的快速分离和免疫分析。
影响因子：
39.3
作者：
He B;Liu S;Wang Y;Xu M;Cai W;Liu J;Bai W;Ye S;Ma Y;Hu H;Meng H;Sun T;Li Y;Luo H;Shi M;Du X;Zhao W;Chen S;Yang J;Zhu H;Jie Y;Yang Y;Guo D;Wang Q;Liu Y;Yan H;Wang M;Chen YQ
通讯作者：
Chen YQ