Human adenoviruses of subgenera B, C, and E with various tropisms differ in both binding to and replication in the epithelial A549 and 293 cells
Human adenoviruses of subgenera B, C, and E with various tropisms differ in both binding to and replication in the epithelial A549 and 293 cells
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DOI：
10.1006/viro.2002.1359
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发表时间：
2002-03-30
期刊：
影响因子：
3.7
通讯作者：
Wadell, G
中科院分区：
文献类型：
--
作者：
Mei, YF;Lindman, K;Wadell, G
研究了腺病毒31 (Ad31) （A亚属）、Ad3、Ad7、Ad11p、Ad11a和Ad35 （B亚属）、Ad5v和Ad5p （C亚属）、Ad37 （D亚属）、Ad4 （E亚属）和Ad41 （F亚属）6个腺病毒亚属。用流式细胞术比较不同腺病毒与293（人肾胚胎细胞）和A549（人肺癌细胞）细胞的相对结合特性。所有分析的腺病毒都以剂量依赖的方式与细胞结合。结合能力表明，Ad11p、Ad35 （B亚属：2）和Ad4 （E亚属）均与A549和293细胞有较强的结合，而B亚属的其他成员和D亚属的Ad37表现出中等的结合能力。A亚属、C亚属和F亚属腺病毒对上皮细胞系的细胞膜制剂具有低亲和力，B亚属2和E亚属腺病毒对上皮细胞系的细胞膜制剂具有高亲和力。利用Ad11p和Ad4进行的相互竞争实验表明，这两种病毒不会相互阻断。抗alphavbeta3和alphavbeta5的抗体降低了Ad5v病毒粒子的结合，轻微削弱了Ad4的结合，但不影响Ad11p与A549细胞表面的结合，Ad11p和Ad35的重组纤维蛋白相互阻断了两种病毒与上皮细胞的结合，但不能阻断Ad4。Ad11p和Ad4的六邻体蛋白表达效率是Ad5载体（pFG140）的100倍，而Ad11p和Ad4的感染性是常用Ad5v载体的40- 200倍。综上所述，我们的研究结果表明，Ad11p和Ad4结合不同的受体分子，这两种病毒的纤维提供了优势的高度结合，这显然是后续内化和有效表达的必要条件。(C) 2002 Elsevier Science （USA）。
Adenoviruses of six subgenera, namely, adenovirus 31 (Ad31) (subgenus A), Ad3, Ad7, Ad11p, Ad11a, and Ad35 (subgenus B), Ad5v and Ad5p (subgenus C), Ad37 (subgenus D), Ad4 (subgenus E), and Ad41 (subgenus F), were studied. The relative binding properties of different adenoviruses to 293 (human kidney embryonic cells) and A549 (human lung carcinoma cells) cells were compared by flow cytometry. All analyzed adenoviruses bound to cells in a dose-dependent manner. The binding capacity showed that Ad11p, Ad35 (subgenus B:2) with kidney tropism, and Ad4 (subgenus E), which can cause adenopharyngoconjunctivitis, bound strongly to both A549 and 293 cells, The other members of subgenus B and Ad37 of subgenus D manifested an intermediate binding capacity. The analyzed adenoviruses of subgenera A, C, and F manifested a low affinity, Adenoviruses of subgenera B:2 and E manifested high binding affinity to preparations of cell membranes from the epithelial cell lines. Reciprocal competition experiments using Ad11p and Ad4 demonstrated that the two viruses did not block each other. Antibodies against alphavbeta3 and alphavbeta5 reduced the binding of Ad5v virions and slightly impaired the binding of Ad4 but did not affect Ad11p binding to the A549 cell surface, Recombinant fiber proteins of Ad11p and Ad35 reciprocally blocked the binding of both viruses to the epithelial cells but they could not block Ad4. The hexon protein expression of Ad11p and Ad4 was 100 times more efficient than that of the Ad5 vector (pFG140), whereas the infectivity of Ad11p and Ad4 was 40- to 200-fold that of the commonly used Ad5v vector. Taken together, our findings demonstrate that Ad11p and Ad4 bind different receptor molecules and that the fibers of these two viruses provide the predominant high degree of binding, which obviously is a requirement for subsequent internalization and efficacious expression. (C) 2002 Elsevier Science (USA).