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首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >A positive-feedback mechanism promotes reovirus particle conversion to the intermediate associated with membrane penetration
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A positive-feedback mechanism promotes reovirus particle conversion to the intermediate associated with membrane penetration

机译：正反馈机制促进呼肠孤病毒颗粒转化为与膜渗透相关的中间体

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摘要

Membrane penetration by reovirus is associated with conversion of a metastable intermediate, the ISVP, to a further-disassembled particle, the ISVP*. Factors that promote this conversion in cells are poorly understood. Here, we report the in vitro characterization of a positive-feedback mechanism for promoting ISVP* conversion. At high particle concentration, conversion approximated second-order kinetics, and products of the reaction operated in trans to promote the conversion of target ISVPs. Pore-forming peptide μ1N, which is released from particles during conversion, was sufficient for promoting activity. A mutant that does not undergo μ1N release failed to exhibit second-order conversion kinetics and also failed to promote conversion of wild-type target ISVPs. Susceptibility of target ISVPs to promotion in trans was temperature dependent and correlated with target stability, suggesting that capsid dynamics are required to expose the interacting epitope. A positive-feedback mechanism of promoting escape from the metastable intermediate has not been reported for other viruses but represents a generalizable device for sensing a confined volume, such as that encountered during cell entry.
机译：呼肠孤病毒的膜渗透与亚稳中间体ISVP向进一步分解的颗粒ISVP *的转化有关。促进细胞中这种转化的因素了解甚少。在这里，我们报告了促进ISVP *转化的正反馈机制的体外表征。在高颗粒浓度下，转化率接近二级动力学，反应产物反式操作以促进目标ISVP的转化。在转化过程中从颗粒释放的成孔肽μ1N足以促进活性。未经历μ1N释放的突变体无法显示二级转化动力学，也无法促进野生型靶标ISVP的转化。靶标ISVPs在反式中的易感性是温度依赖性的，并且与靶标稳定性相关，表明需要衣壳动力学来暴露相互作用的表位。对于其他病毒，尚未报道过促进亚稳中间体逃逸的正反馈机制，但它代表了一种可感测受限体积（例如细胞进入过程中遇到的体积）的通用设备。

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