Mouse respiratory epithelial cells support efficient replication of human rhinovirus
Mouse respiratory epithelial cells support efficient replication of human rhinovirus
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DOI：
10.1099/vir.0.19109-0
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发表时间：
2003-10-01
影响因子：
3.8
通讯作者：
Johnston, SL
中科院分区：
文献类型：
--
作者：
Tuthill, TJ;Papadopoulos, NG;Johnston, SL
人类鼻病毒（HRV）是导致上呼吸道大部分病毒感染的原因。此外，HRV感染与哮喘和其他下呼吸道慢性呼吸道疾病的急性恶化有关。开发新疗法需要 HRV 诱发疾病的小动物模型。然而，现有的 HRV 感染小鼠模型很难使用，并且直到最近，小鼠细胞系还被认为通常不允许 HRV 在体外复制。在本报告中，我们证明次要受体组病毒 HRV1B 可以比小鼠成纤维细胞系 (L) 更有效地在小鼠呼吸道上皮细胞系 (LA-4) 中感染和复制。主要受体组病毒 HRV16 需要人细胞间粘附分子-1 (ICAM-1) 才能进入细胞，因此不能感染 LA-4 细胞。然而，体外转录的 HRV16 RNA 的转染导致病毒 RNA 的复制和感染性病毒的产生。嵌合 ICAM-1 分子（包含小鼠 ICAM-11，胞外结构域 1 和 2 被等效的人结构域取代）的表达，使原本不允许的小鼠呼吸道上皮细胞系易于 HRV16 的进入和有效复制。这些观察结果表明，应继续开发由主要组和次要组 HRV 引起的呼吸道感染的小鼠模型。
Human rhinoviruses (HRV) are responsible for the majority of virus infections of the upper respiratory tract. Furthermore, HRV infection is associated with acute exacerbation of asthma and other chronic respiratory diseases of the lower respiratory tract. A small animal model of HRV-induced disease is required for the development of new therapies. However, existing mouse models of HRV infection are difficult to work with and until recently mouse cell lines were thought to be generally non-permissive for HRV replication in vitro. In this report we demonstrate that a virus of the minor receptor group, HRV1B, can infect and replicate in a mouse respiratory epithelial cell line (LA-4) more efficiently than in a mouse fibroblast cell line (L). The major receptor group virus HRV16 requires human intercellular adhesion molecule-1 (ICAM-1) for cell entry and therefore cannot infect LA-4 cells. However, transfection of in vitro-transcribed HRV16 RNA resulted in the replication of viral RNA and production of infectious virus. Expression of a chimeric ICAM-1 molecule, comprising mouse ICAM-11 with extracellular domains 1 and 2 replaced by the equivalent human domains, rendered the otherwise non-permissive mouse respiratory epithelial cell line susceptible to entry and efficient replication of HRV16. These observations suggest that the development of mouse models of respiratory tract infection by major as well as minor group HRV should be pursued.