The role of the adenovirus protease in virus entry into cells
The role of the adenovirus protease in virus entry into cells
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DOI：
10.1002/j.1460-2075.1996.tb00525.x
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发表时间：
1996-04-15
期刊：
影响因子：
11.4
通讯作者：
Helenius, A
中科院分区：
文献类型：
--
作者：
Greber, UF;Webster, P;Helenius, A
腺病毒脱壳是一个分步的过程，最终通过核孔复合物将病毒DNA释放到细胞核中并解离衣壳。使用定量生物化学，免疫化学和形态学方法，我们证明，半胱氨酸蛋白酶，L3/p23，位于衣壳内的抑制剂块的衣壳稳定蛋白VI的降解，并防止病毒在核膜的脱壳。对病毒内化、纤维脱落和病毒与核膜的结合没有影响。病毒酶（在细胞外病毒中休眠）被两种单独的信号激活，这两种信号都不足以单独激活;病毒与整联蛋白受体的相互作用（用RGD肽抑制）和病毒颗粒重新进入内体或胞质溶胶中的还原环境。缺乏功能性蛋白酶（ts 1）的错误组装突变病毒无法释放纤维并渗透到胞质溶胶中。结果表明，L3/p23不仅需要组装一个进入能力的病毒，而且还需要拆卸传入的病毒。
Adenovirus uncoating is a step,vise process which culminates in the release of the viral DNA into the nucleus through the nuclear pore complexes and dissociation of the capsid. Using quantitative biochemical, immunochemical and morphological methods, we demonstrate that inhibitors of the cysteine protease, L3/p23, located inside the capsid block the degradation of the capsid-stabilizing protein VI, and prevent virus uncoating at the nuclear membrane. There was no effect on virus internalization, fiber shedding and virus binding to the nuclear envelope. The viral enzyme (dormant in the extracellular virus) was activated by two separate signals, neither of which was sufficient alone; virus interaction with the integrin receptor (inhibited with RGD peptides) and re-entry of the virus particle into a reducing environment in the endosome or the cytosol. Incorrectly assembled mutant viruses that lack the functional protease (ts1) failed at releasing fibers and penetrating into the cytosol. The results indicated that L3/p23 is needed not only to assemble an entry-competent virus but also to disassemble the incoming virus.