Phosphoprotein of Human Parainfluenza Virus Type 3 Blocks Autophagosome-Lysosome Fusion to Increase Virus Production
Phosphoprotein of Human Parainfluenza Virus Type 3 Blocks Autophagosome-Lysosome Fusion to Increase Virus Production
复制标题
人副流感病毒 3 型的磷蛋白阻断自噬体-溶酶体融合以增加病毒产量
DOI：
10.1016/j.chom.2014.04.004
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发表时间：
2014-05-14
影响因子：
30.3
通讯作者：
Chen, Mingzhou
中科院分区：
文献类型：
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作者：
Ding, Binbin;Zhang, Guangyuan;Chen, Mingzhou
自噬是一个多步骤的过程，在这个过程中，细胞质成分，包括入侵的病原体，被自噬小体捕获，然后与降解的溶酶体融合。负链RNA病毒，包括副粘病毒，已经被证明可以改变自噬，但其分子机制仍然很大程度上还不清楚。我们证明，人类副流感病毒3型(HPIV3)通过阻断自噬小体-溶酶体融合而诱导不完全自噬，导致病毒产量增加。病毒磷酸蛋白(P)是抑制自噬小体降解的必要条件和充分条件。P与SNAP29结合并抑制其与Synaxin 17的相互作用，从而阻止这两个宿主SNARE蛋白介导自噬小体-溶体融合。不完全自噬和由此产生的自噬小体积累增加了细胞外病毒的产量，但不影响病毒蛋白质的合成。这些发现突显了病毒如何通过破坏SNARE蛋白的功能来阻止自噬小体的降解。
Autophagy is a multistep process in which cytoplasmic components, including invading pathogens, are captured by autophagosomes that subsequently fuse with degradative lysosomes. Negative-strand RNA viruses, including paramyxoviruses, have been shown to alter autophagy, but the molecular mechanisms remain largely unknown. We demonstrate that human parainfluenza virus type 3 (HPIV3) induces incomplete autophagy by blocking autophagosome-lysosome fusion, resulting in increased virus production. The viral phosphoprotein (P) is necessary and sufficient to inhibition autophagosome degradation. P binds to SNAP29 and inhibits its interaction with syntaxin17, thereby preventing these two host SNARE proteins from mediating autophagosome-lysome fusion. Incomplete autophagy and resultant autophagosome accumulation increase extracellular viral production but do not affect viral protein synthesis. These findings highlight how viruses can block autophagosome degradation by disrupting the function of SNARE proteins.