E1A-induced apoptosis does not prevent replication of adenoviruses with deletion of E1b in majority of infected cancer cells
E1A-induced apoptosis does not prevent replication of adenoviruses with deletion of E1b in majority of infected cancer cells
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DOI：
10.1038/sj.cgt.7700739
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发表时间：
2004-09-01
影响因子：
6.4
通讯作者：
Zhou, HS
中科院分区：
文献类型：
--
作者：
Rao, XM;Tseng, MT;Zhou, HS
凋亡途径作为细胞防御机制启动，以消除腺病毒感染的细胞。我们研究了E1A诱导的细胞凋亡如何干扰癌细胞中的病毒复制。我们发现E1B19K单独可以有效地抑制E1A诱导的癌细胞凋亡。E1B19K和E1B55K缺失的病毒导致细胞DNA降解。然而，不到20%的人肺癌细胞感染的病毒删除E1B19 K和E1B55 K有染色质凝聚和多微核形成的证据（凋亡标志），这些细胞不能产生感染性病毒颗粒。大多数的癌细胞感染的病毒删除整个E1b基因没有经历延长的细胞凋亡，并产生丰富的病毒后代。因此，只有一小部分癌细胞发生凋亡，不允许E1b缺失的病毒复制，而大多数癌细胞对E1A诱导的细胞凋亡有抗性，可以支持病毒选择性复制。这项研究的结果表明，除了抑制E1A诱导的细胞凋亡，E1B蛋白可能有助于其他重要的作用，在病毒的生命周期。我们的研究结果还表明，将病毒诱导的凋亡和选择性病毒复制结合到一个载体中将是一种新的破坏癌细胞的方法。
Apoptotic pathways are initiated as a cellular defense mechanism to eliminate adenovirus-infected cells. We have investigated how E1A-induced apoptosis interferes with viral replication in cancer cells. We found that E1B19K alone can efficiently suppress E1A-induced apoptosis in cancer cells. Viruses deleted for both E1B19K and E1B55K resulted in cellular DNA degradation. However, less than 20% of human lung cancer cells infected with a virus deleted for both E1B19K and E1B55 K had evidence of chromatin condensation and multiple-micronuclei formation ( apoptotic hallmarks); these cells could not produce infectious viral particles. The majority of cancer cells infected with viruses deleted for the entire E1b gene did not undergo extended apoptosis and produced abundant viral progeny. Thus, only a fraction of cancer cells underwent apoptosis and did not allow E1b-deleted viruses to replicate, while the majority of cancer cells were resistant to E1A-induced apoptosis and could support virus-selective replication. The results of this study imply that, in addition to inhibiting E1A-induced apoptosis, E1B proteins may contribute other important roles in the viral life cycle. Our results also suggest that combining virus-induced apoptosis and selective viral replication into one vector will be a novel approach to destroy cancer cells.