Organelle-Like Membrane Compartmentalization of Positive-Strand RNA Virus Replication Factories

Boon, Johan A. den; Ahlquist, Paul

doi:10.1146/annurev.micro.112408.134012

Cited by 390 publications

(294 citation statements)

References 108 publications

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“…SFV replication intermediates) might be poor substrates for Dicer due to intrinsic features (e.g. 5′ cap modifications) or due to the fact that they are sequestered inside membrane‐bound replication complexes (“viral factories”) (Miller & Krijnse‐Locker, 2008; den Boon & Ahlquist, 2010). Alternatively, the amplitude and/or kinetics of the dsRNAi response upon virus infection and/or the amount of dsRNA substrate produced by viral replication might not be sufficient to provide effective antiviral protection in the cell types that we studied.…”

Section: Discussionmentioning

confidence: 99%

Inactivation of the type I interferon pathway reveals long double‐stranded RNA‐mediated RNA interference in mammalian cells

et al. 2016

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RNA interference (RNAi) elicited by long double‐stranded (ds) or base‐paired viral RNA constitutes the major mechanism of antiviral defence in plants and invertebrates. In contrast, it is controversial whether it acts in chordates. Rather, in vertebrates, viral RNAs induce a distinct defence system known as the interferon (IFN) response. Here, we tested the possibility that the IFN response masks or inhibits antiviral RNAi in mammalian cells. Consistent with that notion, we find that sequence‐specific gene silencing can be triggered by long dsRNAs in differentiated mouse cells rendered deficient in components of the IFN pathway. This unveiled response is dependent on the canonical RNAi machinery and is lost upon treatment of IFN‐responsive cells with type I IFN. Notably, transfection with long dsRNA specifically vaccinates IFN‐deficient cells against infection with viruses bearing a homologous sequence. Thus, our data reveal that RNAi constitutes an ancient antiviral strategy conserved from plants to mammals that precedes but has not been superseded by vertebrate evolution of the IFN system.

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Section: Discussionmentioning

confidence: 99%

Inactivation of the type I interferon pathway reveals long double‐stranded RNA‐mediated RNA interference in mammalian cells

et al. 2016

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“…For some viruses there is evidence that these compartments are lined with a shell of replicase proteins (25). In the case of SFV, there is no evidence that the spherules contain a replicase protein shell.…”

Section: Discussionmentioning

confidence: 99%

In vitro evolution of high-titer, virus-like vesicles containing a single structural protein

Rose

Buonocore

Schell

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Self-propagating, infectious, virus-like vesicles (VLVs) are generated when an alphavirus RNA replicon expresses the vesicular stomatitis virus glycoprotein (VSV G) as the only structural protein.The mechanism that generates these VLVs lacking a capsid protein has remained a mystery for over 20 years. We present evidence that VLVs arise from membrane-enveloped RNA replication factories (spherules) containing VSV G protein that are largely trapped on the cell surface. After extensive passaging, VLVs evolve to grow to high titers through acquisition of multiple point mutations in their nonstructural replicase proteins. We reconstituted these mutations into a plasmid-based system from which hightiter VLVs can be recovered. One of these mutations generates a late domain motif (PTAP) that is critical for high-titer VLV production. We propose a model in which the VLVs have evolved in vitro to exploit a cellular budding pathway that is hijacked by many enveloped viruses, allowing them to bud efficiently from the cell surface. Our results suggest a basic mechanism of propagation that may have been used by primitive RNA viruses lacking capsid proteins. Capsids may have evolved later to allow more efficient packaging of RNA, greater virus stability, and evasion of innate immunity.VSV glycoprotein | evolution | SFV replicon | late domain

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“…To achieve this, plant viruses use a variety of strategies to suppress or circumvent host defense systems and promote their infection. These include the formation of virusinduced miniorganelles like membranous structures to increase the local concentration of proviral factors and viral RNA template and to sequester newly synthesized viral genomes from host nucleases (22,23), the exploitation of viral suppressors of RNA silencing to block the degradation or translation repression of viral RNAs, and interference with the phytohormone signaling involved in antiviral defense (21). Despite a number of recent advances that unveil mechanisms underlying plant-virus molecular arms race (reviewed in refs.…”

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confidence: 99%

Harnessing host ROS-generating machinery for the robust genome replication of a plant RNA virus

Hyodo

Hashimoto

Kuchitsu

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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As sessile organisms, plants have to accommodate to rapid changes in their surrounding environment. Reactive oxygen species (ROS) act as signaling molecules to transduce biotic and abiotic stimuli into plant stress adaptations. It is established that a respiratory burst oxidase homolog B of Nicotiana benthamiana (NbRBOHB) produces ROS in response to microbe-associated molecular patterns to inhibit pathogen infection. Plant viruses are also known as causative agents of ROS induction in infected plants; however, the function of ROS in plant-virus interactions remains obscure. Here, we show that the replication of red clover necrotic mosaic virus (RCNMV), a plant positive-strand RNA [(+)RNA] virus, requires NbRBOHB-mediated ROS production. The RCNMV replication protein p27 plays a pivotal role in this process, redirecting the subcellular localization of NbRBOHB and a subgroup II calcium-dependent protein kinase of N. benthamiana (NbCDPKiso2) from the plasma membrane to the p27-containing intracellular aggregate structures. p27 also induces an intracellular ROS burst in an RBOH-dependent manner. NbCDPKiso2 was shown to be an activator of the p27-triggered ROS accumulations and to be required for RCNMV replication. Importantly, this RBOH-derived ROS is essential for robust viral RNA replication. The need for RBOHderived ROS was demonstrated for the replication of another (+) RNA virus, brome mosaic virus, suggesting that this characteristic is true for plant (+)RNA viruses. Collectively, our findings revealed a hitherto unknown viral strategy whereby the host ROS-generating machinery is diverted for robust viral RNA replication.positive-strand RNA virus | viral RNA replication | reactive oxygen species | respiratory burst oxidase homolog | calcium-dependent protein kinase P lants have evolved complicated and sophisticated strategies to survive environmental changes. The rapid generation of reactive oxygen species (ROS) is one of the hallmarks of plant responses to various biotic and abiotic stresses (1). Plant NADPH oxidase, termed RBOHs (respiratory burst oxidase homologs), localize at the plasma membrane (PM) and intracellular compartments including the Golgi apparatus (2, 3) and play a key role in ROS production upon the perception of environmental stresses (4). In Nicotiana benthamiana, an RBOHB (NbRBOHB) plays important roles in ROS production triggered by microbe-associated molecular patterns (MAMPs), such as bacterial flagellin and fungal chitin, and facilitates plant immunity against biotrophic pathogens including an oomycete pathogen Phytophthola infestance and tobacco mosaic virus (5-8). RBOH activity is tightly and coordinately regulated posttranslationally [e.g., activation by Ca 2+ , phosphatidic acid (PA), G proteins, or protein kinases] (9-12). It has recently been shown that receptor-like cytoplasmic kinases and calciumdependent protein kinases (CDPKs) regulate RBOHs activity via direct phosphorylation or through modulating regulators of RBOHs during recognition of MAMPs via corresponding surface-loca...

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Organelle-Like Membrane Compartmentalization of Positive-Strand RNA Virus Replication Factories

Cited by 390 publications

References 108 publications

Inactivation of the type I interferon pathway reveals long double‐stranded RNA‐mediated RNA interference in mammalian cells

Inactivation of the type I interferon pathway reveals long double‐stranded RNA‐mediated RNA interference in mammalian cells

In vitro evolution of high-titer, virus-like vesicles containing a single structural protein

Harnessing host ROS-generating machinery for the robust genome replication of a plant RNA virus

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