Basal cells of differentiated bronchial epithelium are more susceptible to rhinovirus infection
Basal cells of differentiated bronchial epithelium are more susceptible to rhinovirus infection
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DOI：
10.1165/rcmb.2007-0050oc
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发表时间：
2008-05-01
影响因子：
6.4
通讯作者：
Gern, James E.
中科院分区：
文献类型：
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作者：
Jakiela, Bogdan;Brockman-Schneider, Rebecca;Gern, James E.
我们使用体外分化的气管-支气管上皮模型来分析不同类型的细胞对鼻病毒(RV)感染的敏感性。对照组的原代细胞在气液界面培养，形成分化的上皮细胞。胰酶消化后分离细胞悬液，分别感染RV16和RVIA血清型。流式细胞仪检测病毒衣壳蛋白VP2的表达，实时定量聚合酶链式反应检测病毒复制，细胞角蛋白14和细胞间黏附分子1(ICAM 1)的表达。与基础以上细胞相比，基底细胞VP2阳性细胞百分率增加(RVIA：37.8%对9.1%，P<；0.01；RV16：12.0对3.0%，P<；0.05)。在基底细胞中，每个细胞的平均病毒RNA拷贝数也高于基底细胞(在感染RV1A和RV16的细胞中，分别增加2.2和2.4倍)。33.3%的基底细胞表达ICAM-1，8.1%的基底细胞表达ICAM-1(P<；0.05)。最后，在上皮损伤的培养模型中(基底上细胞脱落或表面划痕)，与完整的细胞层相比，RVIA的复制明显更多。这些发现表明，基底层细胞比基底层细胞更容易感染RV。对于大型组RV，这可能部分是由于ICAM-1的表达增加；然而，小型组RV在基底细胞中的复制也更有效。这些结果提示，上皮细胞分化可能与抗病毒防御机制的成熟有关。
We used an in vitro model of differentiated tracheolbronchial epithelium to analyze the susceptibility of different cell types to infection with rhinoviruses (RVs). Primary cells from control subjects were cultured in an air-liquid interface to form differentiated epithelia. Suprabasal and basal fractions were separated after trypsin digestion, and cell suspensions were infected with serotypes RV16 and RVIA. These cell fractions were analyzed for expression of viral capsid protein VP2 (flow cytometry), viral replication (real-time PCR), cytolkeratin-14, and intercellular adhesion molecule-1 (ICAM-1). Compared with suprabasal fraction, basal cells had increased percentages of cells staining positive for VP2 (RVIA: 37.8% versus 9.1%, P < 0.01; RV16: 12.0 versus 3.0%, P < 0.05). The average number of viral RNA copies per cell was also higher in basal cells (2.2- and 2.4-fold increase in RV1A- and RV16-infected cells, respectively) compared with suprabasal cells. Furthermore, ICAM-1 was expressed by 33.3% of basal cells, compared with 8.1% of suprabasal cells (P < 0.05). Finally, in culture models of epithelial injury (detached suprabasal cells or scratched surface), there was significantly greater replication of RVIA compared with intact cell layer. These findings demonstrate that basal cells are more susceptible to RV infection than suprabasal cells. For major group RV, this may be in part due to increased expression of ICAM-1; however, minor group RV also replicated more effectively in basal cells. These results suggest the possibility that epithelial cell differentiation is associated with the maturation of antiviral defense mechanisms.