Role of viral vectors and virion shells in cellular gene expression.
Role of viral vectors and virion shells in cellular gene expression.
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病毒载体和病毒颗粒壳在细胞基因表达中的作用。
DOI：
10.1016/j.ymthe.2003.11.007
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Samulski,RichardJude
中科院分区：
文献类型：
--
作者：
Stilwell,JackieL;Samulski,RichardJude
病毒粒子外壳在病毒发病机制中的作用相对未知，但在人类基因转移实验中使用病毒载体需要了解这些相互作用。在这项研究中，我们使用DNA微阵列，以确定在致病性腺病毒或非致病性腺相关病毒感染的基因调制。对野生型病毒、重组载体或空病毒粒子的应答进行了比较。腺相关病毒壳诱导的变化几乎完全由完整的病毒引起。细胞基因引起非致病性反应，抗增殖基因被诱导为一个簇。相比之下，腺病毒和腺病毒空衣壳感染分别产生了更广泛的反应和亚群，包括诱导与致病作用相关的免疫和应激反应基因。我们的研究表明，病毒衣壳对细胞基因表达的影响，以及潜在的宿主毒性，必须考虑独立于载体基因组的安全基因转移在临床上。
The role of the virion shell in viral pathogenesis is relatively unknown yet the use of viral vectors in human gene transfer experiments requires an understanding of these interactions. In this study, we used DNA microarrays to identify genes modulated during pathogenic adenovirus or nonpathogenic adeno-associated virus infections. Responses to wt viruses, recombinant vectors, or empty virion particles were compared. Adeno-associated virus shells induced nearly the full complement of changes elicited by the intact virus. The cellular genes elicited a nonpathogenic response, with antiproliferative genes being induced as a cluster. In contrast, adenovirus and adenovirus empty capsid infection yielded a broader response and subset, respectively, including induction of immune and stress-response genes associated with pathogenic effects. Our studies show that the impact of the viral capsid on cellular gene expression, and potential host toxicity, must be considered independent of the vector genome for safe gene transfer in the clinic.