MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-α treatment.
MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-α treatment.
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DOI：
10.1099/vir.0.052910-0
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发表时间：
2013-08
期刊：
影响因子：
--
通讯作者：
van den Hoogen BG
中科院分区：
文献类型：
--
作者：
de Wilde AH;Raj VS;Oudshoorn D;Bestebroer TM;van Nieuwkoop S;Limpens RWAL;Posthuma CC;van der Meer Y;Bárcena M;Haagmans BL;Snijder EJ;van den Hoogen BG
冠状病毒 (CoV) 感染通常与人类和动物的呼吸道和肠道疾病有关。 2003 年爆发的严重急性呼吸系统综合症 (SARS) 凸显了冠状病毒引起的疾病对人类潜在的致命后果。 2012年，出现了一种新型冠状病毒（中东呼吸综合症冠状病毒；MERS-CoV），迄今为止已导致49人感染病例，其中23人死亡。在这项研究中，我们表征了 MERS-CoV 在人类和猴细胞系中的复制和细胞毒性。受感染的 Vero 细胞的电子显微镜显示了广泛的膜重排，包括双膜囊泡和卷曲膜的形成，这些重排先前已与 SARS-CoV 和其他 CoV 的 RNA 合成有关。感染后，我们观察到病毒 RNA 合成迅速增加，并释放高滴度的感染子代，随后出现明显的细胞病理学变化。这些特征被用来开发一种 96 孔格式的抗病毒化合物筛选测定方法，该方法用于鉴定环孢菌素 A 作为细胞培养物中 MERS-CoV 复制的抑制剂。此外，MERS-CoV 对α干扰素 (IFN-α) 治疗的敏感性比 SARS-CoV 高 50-100 倍，这一观察结果可能对 MERS-CoV 感染患者的治疗具有重要意义。 MERS-CoV 感染并不能阻止 IFN 诱导的磷酸化 STAT1 核易位，而 SARS-CoV 感染则相反，该阻断会抑制抗病毒基因的表达。这些发现强调了这些关系较远的人畜共患冠状病毒在与细胞先天免疫反应的相互作用和逃避方面的相关差异。
Coronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. The 2003 outbreak of severe acute respiratory syndrome (SARS) highlighted the potentially lethal consequences of CoV-induced disease in humans. In 2012, a novel CoV (Middle East Respiratory Syndrome coronavirus; MERS-CoV) emerged, causing 49 human cases thus far, of which 23 had a fatal outcome. In this study, we characterized MERS-CoV replication and cytotoxicity in human and monkey cell lines. Electron microscopy of infected Vero cells revealed extensive membrane rearrangements, including the formation of double-membrane vesicles and convoluted membranes, which have been implicated previously in the RNA synthesis of SARS-CoV and other CoVs. Following infection, we observed rapidly increasing viral RNA synthesis and release of high titres of infectious progeny, followed by a pronounced cytopathology. These characteristics were used to develop an assay for antiviral compound screening in 96-well format, which was used to identify cyclosporin A as an inhibitor of MERS-CoV replication in cell culture. Furthermore, MERS-CoV was found to be 50–100 times more sensitive to alpha interferon (IFN-α) treatment than SARS-CoV, an observation that may have important implications for the treatment of MERS-CoV-infected patients. MERS-CoV infection did not prevent the IFN-induced nuclear translocation of phosphorylated STAT1, in contrast to infection with SARS-CoV where this block inhibits the expression of antiviral genes. These findings highlight relevant differences between these distantly related zoonotic CoVs in terms of their interaction with and evasion of the cellular innate immune response.
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DOI：
10.1016/s0140-6736(03)13967-0
发表时间：
2003-07-26
期刊：
Lancet (London, England)
影响因子：
--
作者：
Kuiken T;Fouchier RA;Schutten M;Rimmelzwaan GF;van Amerongen G;van Riel D;Laman JD;de Jong T;van Doornum G;Lim W;Ling AE;Chan PK;Tam JS;Zambon MC;Gopal R;Drosten C;van der Werf S;Escriou N;Manuguerra JC;Stöhr K;Peiris JS;Osterhaus AD
通讯作者：
Osterhaus AD
影响因子：
5.4
作者：
Gosert, R;Kanjanahaluethai, A;Baker, SC
通讯作者：
Baker, SC
DOI：
10.1073/pnas.57.4.933
发表时间：
1967-01-01
影响因子：
11.1
作者：
MCINTOSH, K;DEES, JH;CHANOCK, RM
通讯作者：
CHANOCK, RM
影响因子：
3.8
作者：
de Wilde, Adriaan H.;Zevenhoven-Dobbe, Jessika C.;van Hemert, Martijn J.
通讯作者：
van Hemert, Martijn J.
影响因子：
7.6
作者：
Paragas, J;Blatt, LM;Endy, TP
通讯作者：
Endy, TP