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      Seeking Membranes: Positive-Strand RNA Virus Replication Complexes

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      Journal: PLoS Biology
      Publisher: Public Library of Science

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          Abstract

          How much do we really understand about how +RNA viruses usurp and transform the intracellular architecture of host cells when they replicate?

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          Most cited references18

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          The lipid droplet is an important organelle for hepatitis C virus production.

          Yusuke Miyanari, Kimie Atsuzawa, Nobuteru Usuda … (2007)
          The lipid droplet (LD) is an organelle that is used for the storage of neutral lipids. It dynamically moves through the cytoplasm, interacting with other organelles, including the endoplasmic reticulum (ER). These interactions are thought to facilitate the transport of lipids and proteins to other organelles. The hepatitis C virus (HCV) is a causative agent of chronic liver diseases. HCV capsid protein (Core) associates with the LD, envelope proteins E1 and E2 reside in the ER lumen, and the viral replicase is assumed to localize on ER-derived membranes. How and where HCV particles are assembled, however, is poorly understood. Here, we show that the LD is involved in the production of infectious virus particles. We demonstrate that Core recruits nonstructural (NS) proteins and replication complexes to LD-associated membranes, and that this recruitment is critical for producing infectious viruses. Furthermore, virus particles were observed in close proximity to LDs, indicating that some steps of virus assembly take place around LDs. This study reveals a novel function of LDs in the assembly of infectious HCV and provides a new perspective on how viruses usurp cellular functions.
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            Modification of intracellular membrane structures for virus replication

            Sven Miller, Jacomine Krijnse-Locker (2008)
            Key Points Plus-stranded RNA viruses induce large membrane structures that might support the replication of their genomes. Similarly, cytoplasmic replication of poxviruses (large DNA viruses) occurs in associated membranes. These membranes originate from the endoplasmic reticulum (ER) or endosomes. Membrane vesicles that support viral replication are induced by a number of RNA viruses. Similarly, the poxvirus replication site is surrounded by a double-membraned cisterna that is derived from the ER. Analogies to autophagy have been proposed since the finding that autophagy cellular processes involve the formation of double-membrane vesicles. However, molecular evidence to support this hypothesis is lacking. Membrane association of the viral replication complex is mediated by the presence of one or more viral proteins that contain sequences which associate with, or integrate into, membranes. Replication-competent membranes might contain viral or cellular proteins that contain amphipathic helices, which could mediate the membrane bending that is required to form spherical vesicles. Whereas poxvirus DNA replication occurs inside the ER-enclosed site, for most RNA viruses the topology of replication is not clear. Preliminary results for some RNA viruses suggest that their replication could also occur inside double-membrane vesicles. We speculate that cytoplasmic replication might occur inside sites that are 'enwrapped' by an ER-derived cisterna, and that these cisternae are open to the cytoplasm. Thus, RNA and DNA viruses could use a common mechanism for replication that involves membrane wrapping by cellular cisternal membranes. We propose that three-dimensional analyses using high-resolution electron-microscopy techniques could be useful for addressing this issue. High-throughput small-interfering-RNA screens should also shed light on molecular requirements for virus-induced membrane modifications.
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              Virus factories: associations of cell organelles for viral replication and morphogenesis

              Reyes R Novoa, Gloria Calderita, Rocío Arranz … (2005)
              Abstract Genome replication and assembly of viruses often takes place in specific intracellular compartments where viral components concentrate, thereby increasing the efficiency of the processes. For a number of viruses the formation of ‘factories’ has been described, which consist of perinuclear or cytoplasmic foci that mostly exclude host proteins and organelles but recruit specific cell organelles, building a unique structure. The formation of the viral factory involves a number of complex interactions and signalling events between viral and cell factors. Mitochondria, cytoplasmic membranes and cytoskeletal components frequently participate in the formation of viral factories, supplying basic and common needs for key steps in the viral replication cycle.
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                Author and article information

                Journal
                Journal ID (nlm-ta): PLoS Biol
                Journal ID (publisher-id): pbio
                Journal ID (publisher-id): plbi
                Journal ID (pmc): plosbiol
                Title: PLoS Biology
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Print): 1544-9173
                ISSN (Electronic): 1545-7885
                Publication date (Print): October 2008
                Publication date (Electronic): 28 October 2008
                Volume: 6
                Issue: 10
                Electronic Location Identifier: e270
                Article
                Publisher ID: 08-PLBI-P-3557R2
                DOI: 10.1371/journal.pbio.0060270
                PMC ID: 2573941
                PubMed ID: 18959488
                SO-VID: e062ae29-8fd6-4a5d-aad8-90bbcf963c6b
                Copyright statement: Copyright: © 2008 Mark R. Denison. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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                Related
                SARS-Coronavirus Replication Is Supported by a Reticulovesicular Network of Modified Endoplasmic Reticulum
                Page count
                Pages: 3
                Categories
                Subject: Primer
                Subject: Cell Biology
                Subject: Virology
                Custom metadata
                citation Denison MR (2008) Seeking membranes: Positive-strand RNA virus replication complexes. PLoS Biol 6(10): e270. doi: 10.1371/journal.pbio.0060270

                ScienceOpen disciplines: Life sciences
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                ScienceOpen disciplines: Life sciences

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