Topology of Double-Membraned Vesicles and the Opportunity for Non-Lytic Release of Cytoplasm

• Published in: Autophagy 2005-10, Vol.1 (3), p.182-184
• Main Authors: Kirkegaard, Karla, Jackson, William T.
• Format: Article
• Language: English
• Subjects: Animals; Autophagy; Autophagy-Related Protein 12; Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cycle; Cytoplasm - physiology; Cytoplasmic Vesicles - physiology; Humans; Intracellular Membranes - physiology; Landes; Lysosomal-Associated Membrane Protein 1 - metabolism; Microtubule-Associated Proteins - metabolism; Organogenesis; Phagosomes - physiology; Poliovirus - metabolism; Poliovirus - physiology; Proteins; Proteins - metabolism; RNA Interference; RNA, Viral - metabolism; Small Ubiquitin-Related Modifier Proteins; Virus Replication
• ISSN: 1554-8627; 1554-8635
• DOI: 10.4161/auto.1.3.2065

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 Biology 3: 861-871, 2005) chronicled several similarities between poliovirus-induced membranes andautophagosomes, 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 Atg12p 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.