A role for molecular chaperone Hsc70 in reovirus outer capsid disassembly
A role for molecular chaperone Hsc70 in reovirus outer capsid disassembly
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DOI：
10.1074/jbc.m610258200
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发表时间：
2007-04-20
影响因子：
4.8
通讯作者：
Nibert, Max L.
中科院分区：
文献类型：
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作者：
Ivanovic, Tijana;Agosto, Melina A.;Nibert, Max L.
大多数动物病毒在进入细胞过程中穿过细胞膜屏障后，必须经过进一步的分解才能开始病毒基因表达。在许多情况下，这些拆卸机制仍然定义不清。在本报告中，我们研究了哺乳动物呼肠孤病毒外衣壳分解的最后一步：细胞质释放膜穿透蛋白mu 1的中央三角洲片段，以产生转录活性的病毒核心颗粒。用网织红细胞裂解液进行的体外实验再现了完整的δ分子的释放。该系统的活性要求包括蛋白质因子、ATP、Mg2+和K+离子，这与Hsc70等分子伴侣的参与是一致的。Hsc70和Hsp70的免疫缺失会损害delta的释放，然后通过添加纯化的Hsc70来恢复。Hsc70不仅在裂解物中，而且在细胞进入过程中与释放的δ分子相关。我们得出结论，Hsc70在呼肠孤病毒的外衣壳分解中起着明确的作用，在膜穿透期间或之后不久，为进入颗粒的基因表达和复制做准备。
After crossing the cellular membrane barrier during cell entry, most animal viruses must undergo further disassembly before initiating viral gene expression. In many cases, these disassembly mechanisms remain poorly defined. For this report, we examined a final step in disassembly of the mammalian reovirus outer capsid: cytoplasmic release of the central, delta fragment of membrane penetration protein mu 1 to yield the transcriptionally active viral core particle. An in vitro assay with reticulocyte lysate recapitulated the release of intact delta molecules. Requirements for activity in this system were shown to include a protein factor, ATP, and Mg2+ and K+ ions, consistent with involvement of a molecular chaperone such as Hsc70. Immunodepletion of Hsc70 and Hsp70 impaired delta release, which was then rescued by addition of purified Hsc70. Hsc70 was associated with released delta molecules not only in the lysate but also during cell entry. We conclude that Hsc70 plays a defined role in reovirus outer capsid disassembly, during or soon after membrane penetration, to prepare the entering particle for gene expression and replication.