Role of nucleolin in human parainfluenza virus type 3 infection of human lung epithelial cells
Role of nucleolin in human parainfluenza virus type 3 infection of human lung epithelial cells
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DOI：
10.1128/jvi.78.15.8146-8158.2004
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发表时间：
2004-08-01
影响因子：
5.4
通讯作者：
Banerjee, AK
中科院分区：
文献类型：
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作者：
Bose, S;Basu, M;Banerjee, AK
人类副流感病毒 3 型 (HPIV-3) 是一种空气传播的病原体，可从顶端（管腔）质膜区域感染人类肺上皮细胞。在本研究中，我们发现细胞表面表达的核仁素是 HPIV-3 有效进入人肺上皮 A549 细胞所需的细胞辅助因子。核仁素富集在 A549 细胞的顶端细胞表面区域，HPIV-3 在进入过程中与核仁素相互作用。核仁素在 HPIV-3 复制过程中的重要性通过以下观察得到证实：(i) 用抗核仁素抗体预处理细胞和 (ii) 在将 HPIV-3 添加到细胞之前将其与纯化的核仁素预温育后，HPIV-3 复制受到显着抑制。此外，在抗核蛋白抗体和纯化核蛋白存在的情况下进行的HPIV-3细胞内化和附着测定揭示了HPIV-3内化过程中对核仁素的需求，但在附着过程中则不然。因此，这些结果表明人肺上皮A549细胞表面表达的核仁素在HPIV-3细胞进入过程中发挥重要作用。
Human parainfluenza virus type 3 (HPIV-3) is an airborne pathogen that infects human lung epithelial cells from the apical (luminal) plasma membrane domain. In the present study, we have identified cell surface-expressed nucleolin as a cellular cofactor required for the efficient cellular entry of HPIV-3 into human lung epithelial A549 cells. Nucleolin was enriched on the apical cell surface domain of A549 cells, and HPIV-3 interacted with nucleolin during entry. The importance of nucleolin during HPIV-3 replication was borne out by the observation that HPIV-3 replication was significantly inhibited following (i) pretreatment of cells with antinucleollin antibodies and (ii) preincubation of HPIV-3 with purified nucleolin prior to its addition to the cells. Moreover, HPIV-3 cellular internalization and attachment assays performed in the presence of anti-nucleolin antibodies and purified nucleolin revealed the requirement of nucleolin during HPIV-3 internalization but not during attachment. Thus, these results suggest that nucleollin expressed on the surfaces of human lung epithelial A549 cells plays an important role during HPIV-3 cellular entry.