Modeling pathogenesis of emergent and pre-emergent human coronaviruses in mice.
Modeling pathogenesis of emergent and pre-emergent human coronaviruses in mice.
复制标题
DOI：
10.1007/s00335-018-9760-9
复制
发表时间：
2018-08
期刊：
影响因子：
--
通讯作者：
Baric RS
中科院分区：
文献类型：
--
作者：
Cockrell AS;Leist SR;Douglas MG;Baric RS
过去二十年来，高致病性人类冠状病毒（hcov）的出现表明，它们有可能在人群中造成高发病率和死亡率，并扰乱全球经济。全球大流行的担忧源于它们的高死亡率、通过呼吸道传播的人际传播能力以及完全缺乏经批准的治疗对策。由于hCoV感染的急性病因，限制疾病可能需要开发病毒导向和宿主导向的治疗策略。因此，了解hcov -宿主相互作用如何导致致病性结果依赖于哺乳动物模型，这些模型密切概括了hcov在人类中的发病机制。实用主义在很大程度上推动了小鼠作为阐明控制发病机制的hcov -宿主相互作用的高效哺乳动物模型的基础。值得注意的是，可处理的小鼠遗传与hCoV反向遗传系统相结合，可以同时操纵病毒和宿主遗传，以评估疾病中病毒-宿主相互作用网络。除了评估已知hcov的病因外，小鼠模型作为评估与出现前cov相关的潜在疾病表型的工具具有临床预测价值。在冠状病毒跨越物种屏障进入人群之前了解其致病性潜力，为解决全球病原体防范提供了一个非常理想的临床前平台，这是世界卫生组织的一项总体指示。尽管我们认识到在强大的小鼠模型中获得的结果需要在非人类灵长类动物中进行评估，但我们将重点关注hCoV小鼠模型的现状，它们作为可处理的复杂遗传生物用于解开复杂的hCoV -宿主相互作用，以及作为临床前评估新治疗干预措施的发病机制模型。
The emergence of highly pathogenic human coronaviruses (hCoVs) in the last two decades has illuminated their potential to cause high morbidity and mortality in human populations and disrupt global economies. Global pandemic concerns stem from their high mortality rates, capacity for human-to-human spread by respiratory transmission, and complete lack of approved therapeutic countermeasures. Limiting disease may require the development of virus-directed and host-directed therapeutic strategies due to the acute etiology of hCoV infections. Therefore, understanding how hCoV–host interactions cause pathogenic outcomes relies upon mammalian models that closely recapitulate the pathogenesis of hCoVs in humans. Pragmatism has largely been the driving force underpinning mice as highly effective mammalian models for elucidating hCoV–host interactions that govern pathogenesis. Notably, tractable mouse genetics combined with hCoV reverse genetic systems has afforded the concomitant manipulation of virus and host genetics to evaluate virus–host interaction networks in disease. In addition to assessing etiologies of known hCoVs, mouse models have clinically predictive value as tools to appraise potential disease phenotypes associated with pre-emergent CoVs. Knowledge of CoV pathogenic potential before it crosses the species barrier into the human population provides a highly desirable preclinical platform for addressing global pathogen preparedness, an overarching directive of the World Health Organization. Although we recognize that results obtained in robust mouse models require evaluation in non-human primates, we focus this review on the current state of hCoV mouse models, their use as tractable complex genetic organisms for untangling complex hCoV–host interactions, and as pathogenesis models for preclinical evaluation of novel therapeutic interventions.
登录
查看更多内容
影响因子：
6.4
作者：
Agnihothram S;Yount BL Jr;Donaldson EF;Huynh J;Menachery VD;Gralinski LE;Graham RL;Becker MM;Tomar S;Scobey TD;Osswald HL;Whitmore A;Gopal R;Ghosh AK;Mesecar A;Zambon M;Heise M;Denison MR;Baric RS
通讯作者：
Baric RS
影响因子：
30.8
作者：
Chan VS;Chan KY;Chen Y;Poon LL;Cheung AN;Zheng B;Chan KH;Mak W;Ngan HY;Xu X;Screaton G;Tam PK;Austyn JM;Chan LC;Yip SP;Peiris M;Khoo US;Lin CL
通讯作者：
Lin CL
DOI：
10.1038/nrmicro.2016.81
发表时间：
2016-08
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
de Wit E;van Doremalen N;Falzarano D;Munster VJ
通讯作者：
Munster VJ
影响因子：
5.4
作者：
Cockrell, Adam S.;Peck, Kayla M.;Heise, Mark T.
通讯作者：
Heise, Mark T.
影响因子：
6.7
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
通讯作者：
Munster VJ