Chimpanzee adenovirus CV-68 adapted as a gene delivery vector interacts with the coxsackievirus and adenovirus receptor

Chimpanzee adenovirus CV-68 adapted as a gene delivery vector interacts with the coxsackievirus and adenovirus receptor
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DOI:
10.1099/0022-1317-83-1-151
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发表时间:
2002-01-01
影响因子:
3.8
通讯作者:
Bergelson, JM
Bergelson, JM
中科院分区:
医学3区
文献类型:
--
作者:
Cohen, CJ;Xiang, ZQ;Bergelson, JM

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黑猩猩腺病毒 68 型 (C68) 的复制缺陷型已被开发出来,以规避对常见人类腺病毒载体的广泛预先存在的免疫力所带来的问题。为了研究 C68 趋向性的决定因素,研究了它与柯萨奇病毒和腺病毒受体 (CAR) 的相互作用。尽管 CHO 细胞对 C68 以及 5 型腺病毒 (Ad5) 的转导具有抗性,但表达人或鼠 CAR 的 CHO 细胞很容易转导。与 Ad5 转导一样,当细胞暴露于抗 CAR 抗体或病毒暴露于可溶形式的 CAR 胞外结构域时,C68 转导会被阻断。这些结果表明 C68 的基因传递是通过 CAR 依赖性机制发生的。
A replication-defective form of chimpanzee adenovirus type 68 (C68) has been developed to circumvent problems posed by widespread preexisting immunity to common human adenovirus vectors. To investigate the determinants of C68 tropism, its interaction with the coxsackievirus and adenovirus receptor (CAR) was studied. Although CHO cells were resistant to transduction by C68 as well as by adenovirus type 5 (Ad5), CHO cells expressing either human or murine CAR were transduced readily. C68 transduction, like Ad5 transduction, was blocked when cells were exposed to anti-CAR antibody or when virus was exposed to a soluble form of the CAR extracellular domain. These results indicate that gene delivery by C68 occurs by a CAR-dependent mechanism.