Topology of double-membraned vesicles and the opportunity for non-lytic release of cytoplasm
Topology of double-membraned vesicles and the opportunity for non-lytic release of cytoplasm
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DOI：
10.4161/auto.1.3.2065
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发表时间：
2005-10-01
期刊：
影响因子：
13.3
通讯作者：
Jackson, William T.
中科院分区：
文献类型：
--
作者：
Kirkegaard, Karla;Jackson, William T.
几种正链RNA病毒感染哺乳动物细胞可诱导双膜小泡，其胞浆表面可作为病毒RNA复制的平台。我们最近的出版物(杰克逊等人)PLOS Biol 2005；3：861-71)记录了脊髓灰质炎病毒诱导的膜和自噬小体之间的几个相似之处，包括诱导GFP-LC3和LAMP1的共同定位。偶尔，这些结构的胞液管腔也含有病毒颗粒；这可能是由于新形成的双层膜包裹了胞浆，胞液在感染后期可能包含高病毒浓度。有趣的是，降低LC3或ATG 12p浓度的RNAi处理对细胞外病毒产量的影响甚至比对细胞内病毒的影响更大。人们通常认为，脊髓灰质炎病毒等无包膜病毒的退出需要细胞裂解。然而，我们假设，自噬体样双膜在成熟后可以变成单膜，为观察到的细胞质病毒的非裂解释放提供了一种长期寻找的机制，可能还有其他细胞质材料抵抗成熟的自噬小体的环境。
Infection of mammalian cells with several positive-strand RNA viruses induces double-membraned vesicles whose cytosolic surfaces serve as platforms for viral RNA replication. Our recent publication (Jackson et al. PLoS Biol 2005; 3:861-71) chronicled several similarities between poliovirus-induced membranes and autophagosomes, including induced co-localization of GFP-LC3 and LAMP1. Occasionally, the cytosolic lumen of these structures also contains viral particles; this likely results from wrapping of cytosol, which can contain high viral concentrations late in infection, by newly formed double membranes. Interestingly, RNAi treatment to reduce LC3 or Atg 12p concentrations reduced yields of extracellular virus even more than intracellular virus. It is often assumed that exit of non-enveloped viruses such as poliovirus requires cell lysis. However, we hypothesize that autophagosome-like double-membranes, which can become single-membraned upon maturation, provide a long-sought mechanism for the observed non-lytic release of cytoplasmic viruses and possibly other cytoplasmic material resistant to the environment of maturing autophagosomes.