In vitro and in vivo biology of recombinant adenovirus vectors with E1, E1/E2A, or E1/E4 deleted
In vitro and in vivo biology of recombinant adenovirus vectors with E1, E1/E2A, or E1/E4 deleted
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DOI：
10.1128/jvi.72.3.2022-2032.1998
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发表时间：
1998-03-01
影响因子：
5.4
通讯作者：
Mehtali, M
中科院分区：
文献类型：
--
作者：
Lusky, M;Christ, M;Mehtali, M
在E1，E1和E2A或E1和E4中有缺陷的等源性E3删除的腺病毒载体在表达E1，E1和E2A或E1和E4的补体细胞系中产生，并在体外和体内表征。在没有互补的情况下，E1和E2A的缺失完全消除了早期和晚期病毒基因的表达，而E1和E4的缺失受损了病毒基因的表达，尽管在较低的水平上，比E1/E2A缺失，在体内持久性，在没有转基因的病毒基因组的选定小鼠菌株中监测了这三种类型的载体，以排除任何干扰免疫原性转基因编码的产物，我们的研究表明，在短期维持和长期维持和长期维持和长期（4个月）病毒DNA在肝脏和肺细胞中的长期持久性和免疫缺陷小鼠的肺细胞的持久性，所有载体都诱导了病毒DNA的长期差异。类似的抗体反应和可比水平的腺病毒特异性细胞毒性T淋巴细胞。这些结果表明，在没有转基因的情况下，腺病毒基因组的进行性缺失不会扩展转导细胞的体内持久性，也不会减少抗病毒免疫反应，此外，我们的数据还确认，在没有经元元素表达的情况下， ，小鼠细胞对病毒抗原的免疫在逐步消除病毒基因组中起较小的作用。
Isogenic, E3-deleted adenovirus vectors defective in E1, E1 and E2A or E1 and E4 were generated in complementation cell lines expressing E1, E1 and E2A or E1 and E4 and characterized in vitro and in vivo. In the absence of complementation, deletion of both E1 and E2A completely abolished expression of early and late viral genes, while deletion of E1 and E4 impaired expression of viral genes, although at a lower level than the E1/E2A deletion, The in vivo persistence of these three types of vectors was monitored in selected strains of mice with viral genomes devoid of transgenes to exclude any interference by immunogenic transgene-encoded products, Our studies showed no significant differences among the vectors in the short-term maintenance and long-term (4-month) persistence of viral DNA in liver and lung cells of immunocompetent and immunodeficient mice, Furthermore, all vectors induced similar antibody responses and comparable levels of adenovirus-specific cytotoxic T lymphocytes. These results suggest that in the absence of transgenes, the progressive deletion of the adenovirus genome does not extend the in vivo persistence of the transduced cells and does not reduce the antivirus immune response, In addition our data confirm that, in the absence of transgene expression, mouse cellular immunity to viral antigens plays a minor role in the progressive elimination of the virus genome.