Infection with MERS-CoV causes lethal pneumonia in the common marmoset.
Infection with MERS-CoV causes lethal pneumonia in the common marmoset.
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DOI：
10.1371/journal.ppat.1004250
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发表时间：
2014-08
期刊：
影响因子：
6.7
通讯作者：
Munster VJ
中科院分区：
文献类型：
--
作者：
Falzarano D;de Wit E;Feldmann F;Rasmussen AL;Okumura A;Peng X;Thomas MJ;van Doremalen N;Haddock E;Nagy L;LaCasse R;Liu T;Zhu J;McLellan JS;Scott DP;Katze MG;Feldmann H;Munster VJ
建立健全的疾病模型对于制定中东呼吸综合征冠状病毒（MERS-CoV）对策至关重要。虽然已经建立了MERS-CoV恒河猴模型，但该模型中缺乏统一的严重疾病，使对策研究的分析复杂化。MERS-CoV刺突糖蛋白与其受体二肽基肽酶4之间相互作用的建模预测了普通狨猴和人类之间相似的相互作用能。通过气管、鼻、口、眼四种途径联合接种，检验绒猴作为MERS-CoV模型的适宜性。大多数狨猴患上了进行性严重肺炎，导致一些动物安乐死。在接种后不同时间点死亡的所有动物的肺部都有明显的广泛病变。有些动物也有病毒血症；在所有感染动物的肺部检测到高病毒载量，并且总RNAseq显示诱导免疫和炎症途径。这是对中东呼吸综合征冠状病毒严重、部分致死疾病模型的首次描述，因此将对评估疫苗和治疗策略的效力以及进行更详细的发病机制研究的能力产生重大影响。强大的动物疾病模型能够准确地描述在人类中观察到的疾病，这有助于疫苗和治疗策略的发展。在这里，我们使用普通狨猴描述了一种新的改进的中东呼吸综合征冠状病毒模型，其中再现了在许多人类病例中观察到的严重甚至致命的疾病。在开发该模型之前，中东呼吸综合征冠状病毒感染的唯一可用动物模型是恒河猴和小鼠模型，后者需要腺病毒转导表达病毒进入所需的人类蛋白。恒河猴模型更接近于模拟在一些患者中观察到的轻度至中度疾病，主要是那些没有明显合并症的患者。普通狨猴模型中疾病严重程度的增加是评估中东呼吸综合征冠状病毒潜在治疗剂能力的重要进展，因为成功治疗的动物和对照动物之间的区别应该更加明显。此外，模型越接近概括在人类中观察到的疾病，研究结果就越有可能最终转化为人类的应用。
The availability of a robust disease model is essential for the development of countermeasures for Middle East respiratory syndrome coronavirus (MERS-CoV). While a rhesus macaque model of MERS-CoV has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. Modeling of the interaction between the MERS-CoV spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and humans. The suitability of the marmoset as a MERS-CoV model was tested by inoculation via combined intratracheal, intranasal, oral and ocular routes. Most of the marmosets developed a progressive severe pneumonia leading to euthanasia of some animals. Extensive lesions were evident in the lungs of all animals necropsied at different time points post inoculation. Some animals were also viremic; high viral loads were detected in the lungs of all infected animals, and total RNAseq demonstrated the induction of immune and inflammatory pathways. This is the first description of a severe, partially lethal, disease model of MERS-CoV, and as such will have a major impact on the ability to assess the efficacy of vaccines and treatment strategies as well as allowing more detailed pathogenesis studies. The development of vaccines and treatment strategies is aided by robust animal disease models that accurately depict the illness that is observed in humans. Here we describe a new, improved model for MERS-CoV using the common marmoset, whereby the severe, and even lethal, illness that has been observed in many human cases is recapitulated. Prior to the development of this model, the only available animal models for MERS-CoV infection were the rhesus macaque and a mouse model that requires adenovirus-transduced expression of the human version of the protein required for virus entry. The rhesus macaque model more closely mimics the mild to moderate disease observed in some patients—mainly those without significant comorbidities. The increased severity of illness in the common marmoset model is an important advance in the ability to evaluate potential therapeutic agents against MERS-CoV, as discrimination between successfully treated and control animals should be more apparent. In addition, the closer models recapitulate the disease observed in humans, the more likely findings can be eventually translated into use in humans.
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影响因子：
5.4
作者：
Niemeyer, Daniela;Zillinger, Thomas;Mueller, Marcel A.
通讯作者：
Mueller, Marcel A.
DOI：
10.1002/prot.10550
发表时间：
2003-01-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
Petrey, D;Xiang, ZX;Honig, B
通讯作者：
Honig, B
影响因子：
5.4
作者：
Page, Carly;Goicochea, Lindsay;Frieman, Matthew
通讯作者：
Frieman, Matthew
影响因子：
14.9
作者：
McCarthy DJ;Chen Y;Smyth GK
通讯作者：
Smyth GK
影响因子：
6.4
作者：
Gralinski LE;Bankhead A 3rd;Jeng S;Menachery VD;Proll S;Belisle SE;Matzke M;Webb-Robertson BJ;Luna ML;Shukla AK;Ferris MT;Bolles M;Chang J;Aicher L;Waters KM;Smith RD;Metz TO;Law GL;Katze MG;McWeeney S;Baric RS
通讯作者：
Baric RS