Role of Microtubules in Extracellular Release of Poliovirus
Role of Microtubules in Extracellular Release of Poliovirus
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DOI：
10.1128/jvi.01819-08
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发表时间：
2009-07-01
影响因子：
5.4
通讯作者：
Jackson, William T.
中科院分区：
文献类型：
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作者：
Taylor, Matthew P.;Burgon, Trever B.;Jackson, William T.
细胞自噬是一种通过形成双膜囊泡将胞质内容物引导到内体和溶酶体途径的过程，是对许多细胞内病原体的先天免疫的一个重要方面。然而，越来越多的证据表明，某些RNA病毒，如脊髓灰质炎病毒，破坏了这一途径，促进了病毒的生长。与细胞自噬体不同，野生型脊髓灰质炎病毒感染诱导的自噬体样膜相对不动。它们的移动性在诺可达唑治疗后增加，这表明囊泡栓系是微管依赖的。在与宿主细胞骨架和分泌途径相互作用有缺陷的突变病毒感染的细胞中，囊泡运动增加，表明栓系减少。在所有情况下，栓系的释放与细胞外病毒数量的增加相关，这与双膜结构捕获的少量细胞质溶胶和病毒可以通过与质膜融合而释放的假设是一致的。我们建议将这种细胞质内容物的细胞外递送称为自噬体介导的无裂解退出（AWOL）。这一途径可以解释在明显没有细胞裂解的情况下，其他细胞质大分子复合物（包括感染因子和聚集蛋白复合物）的退出。
Cellular autophagy, a process that directs cytosolic contents to the endosomal and lysosomal pathways via the formation of double-membraned vesicles, is a crucial aspect of innate immunity to many intracellular pathogens. However, evidence is accumulating that certain RNA viruses, such as poliovirus, subvert this pathway to facilitate viral growth. The autophagosome-like membranes induced during infection with wild-type poliovirus were found to be, unlike cellular autophagosomes, relatively immobile. Their mobility increased upon nocodazole treatment, arguing that vesicular tethering is microtubule dependent. In cells infected with a mutant virus that is defective in its interaction with the host cytoskeleton and secretory pathway, vesicle movement increased, indicating reduced tethering. In all cases, the release of tethering correlated with increased amounts of extracellular virus, which is consistent with the hypothesis that small amounts of cytosol and virus entrapped by double-membraned structures could be released via fusion with the plasma membrane. We propose that this extracellular delivery of cytoplasmic contents be termed autophagosome-mediated exit without lysis (AWOL). This pathway could explain the observed exit, in the apparent absence of cellular lysis, of other cytoplasmic macromolecular complexes, including infectious agents and complexes of aggregated proteins.