Adaptation of an ICAM-1-tropic enterovirus to the mouse respiratory tract.
Adaptation of an ICAM-1-tropic enterovirus to the mouse respiratory tract.
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ICAM-1 嗜性肠道病毒对小鼠呼吸道的适应。
DOI：
10.1128/jvi.01502-10
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发表时间：
2011
影响因子：
5.4
通讯作者：
Gromeier,Matthias
中科院分区：
文献类型：
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作者：
Wang,EricS;Dobrikova,Elena;Goetz,Christian;Dufresne,AndrewT;Gromeier,Matthias
由小核糖核酸病毒科的肠道病毒（EV）属的成员引起的呼吸道（RT）感染是普通感冒的最常见原因，也是慢性肺部疾病恶化的主要因素。缺乏一个实用的小动物模型，这些感染阻碍了洞察普通感冒的致病机制及其在慢性RT疾病中的作用，并阻碍了抗病毒策略的临床前评价。尽管做出了重大努力，但很难设计出在RT中表现出病毒复制的啮齿动物模型。这主要是由于啮齿动物细胞中具有RT向性的EV的众所周知的细胞内宿主限制。我们报告了引起感冒的柯萨奇病毒A21的变异体的进化，柯萨奇病毒A21是一种对人细胞间粘附分子1（hICAM-1）具有嗜性的EV，通过在hICAM-1基因转基因小鼠的肺中连续传代。该过程伴随着病毒基因组的多重变化，表明嗜hICAM-1肠道病毒对RT内特定生长条件的精细适应。在小鼠RT适应的体内，变异型柯萨奇病毒A21在hICAM-1转基因小鼠的肺中表现出复制能力，为阐明EV-宿主在小鼠RT中的相互作用提供了基础。
Respiratory tract (RT) infections by members of the enterovirus (EV) genus of the Picornaviridae family are the most frequent cause for the common cold and a major factor in the exacerbation of chronic pulmonary diseases. The lack of a practical small-animal model for these infections has obstructed insight into pathogenic mechanisms of the common cold and their role in chronic RT illness and has hampered preclinical evaluation of antiviral strategies. Despite significant efforts, it has been difficult to devise rodent models that exhibit viral replication in the RT. This is due mainly to well-known intracellular host restrictions of EVs with RT tropism in rodent cells. We report the evolution of variants of the common-cold-causing coxsackievirus A21, an EV with tropism for the human intercellular adhesion molecule 1 (hICAM-1), through serial passage in the lungs of mice transgenic for thehICAM-1gene. This process was accompanied by multiple changes in the viral genome, suggesting exquisite adaptation of hICAM-1-tropic enteroviruses to the specific growth conditions within the RT. In vivo mouse RT-adapted, variant coxsackievirus A21 exhibited replication competence in the lungs ofhICAM-1transgenic mice, providing a basis for unraveling EV-host interactions in the mouse RT.