Structural insights into the coupling of virion assembly and rotavirus replication

Trask, Shane D.; McDonald, Sarah; Patton, John T.

doi:10.1038/nrmicro2673

Cited by 204 publications

(270 citation statements)

References 107 publications

(219 reference statements)

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“…For rotaviruses, important pediatric gastrointestinal pathogens, it is known that the first steps in the viral lifecycle entail (i) uncoating of virions to create double-layered particles (DLPs) and (ii) induction of DLPs to transcribe viral RNAs [14]. Here we show that rotavirus uncoating and transcription can be recapitulated in vitro on SiN chips and directly visualized by EM.…”

Section: Introductionmentioning

confidence: 88%

Molecular Surveillance of Viral Processes Using Silicon Nitride Membranes

et al. 2013

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Abstract:Here we present new applications for silicon nitride (SiN) membranes to evaluate biological processes. We determined that 50-nanometer thin films of SiN produced from silicon wafers were sufficiently durable to bind active rotavirus assemblies. A direct comparison of SiN microchips with conventional carbon support films indicated that SiN performs equivalent to the traditional substrate to prepare samples for Electron Microscopy (EM) imaging. Likewise, SiN films coated with Ni-NTA affinity layers concentrated rotavirus particles similarly to affinity-coated carbon films. However, affinity-coated SiN membranes outperformed glow-discharged conventional carbon films 5-fold as indicated by the number of viral particles quantified in EM images. In addition, we were able to recapitulate viral uncoating and transcription mechanisms directed onto the microchip surfaces. EM images of these processes revealed the production of RNA transcripts emerging from active rotavirus complexes. These results were confirmed by the functional incorporation of radiolabeled nucleotides into the nascent RNA transcripts. Collectively, we demonstrate new uses for SiN membranes to perform molecular surveillance on life processes in real-time. OPEN ACCESSMicromachines 2013, 4 91

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Section: Introductionmentioning

confidence: 88%

Molecular Surveillance of Viral Processes Using Silicon Nitride Membranes

et al. 2013

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“…Moreover, phylogenetic evidence of long distance dispersal and transmission has been revealed by comparing the protein coding sequences S1, S2 and S4 in Piscine reovirus genomic segments between farmed and wild Atlantic salmon [98]. As an ideal model system for studying the cell entry mechanism used by nonenveloped viruses, single-particle cryo-electron microscopy has been used to observe the 3.3 Å structure of the primed, infectious subvirion GCRV particle, thereby providing structural insight into the coupling of virion assembly [99,100]. Additionally, new insight into the mechanisms of viral factory formation and pathogenesis of aquareoviruses has been acquired from functional studies on aquareoviral genes where NS80, a nonstructural protein of fish reovirus, has been confirmed to be crucial for recruiting viral components to form aquareoviral factories [101].…”

Section: Aquareovirus Genomesmentioning

confidence: 99%

Virus genomes and virus-host interactions in aquaculture animals

Zhang

Gui

2015

Sci. China Life Sci.

172

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Over the last 30 years, aquaculture has become the fastest growing form of agriculture production in the world, but its development has been hampered by a diverse range of pathogenic viruses. During the last decade, a large number of viruses from aquatic animals have been identified, and more than 100 viral genomes have been sequenced and genetically characterized. These advances are leading to better understanding about antiviral mechanisms and the types of interaction occurring between aquatic viruses and their hosts. Here, based on our research experience of more than 20 years, we review the wealth of genetic and genomic information from studies on a diverse range of aquatic viruses, including iridoviruses, herpesviruses, reoviruses, and rhabdoviruses, and outline some major advances in our understanding of virus-host interactions in animals used in aquaculture.

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“…The innermost layer, the core shell, surrounds the viral dsRNA genome and is composed of 120 copies of VP2, formed by dimers 11 .…”

Section: Protein Functionsmentioning

confidence: 99%

“…It is required for the outer capsid assembly and is a transmembrane glycoprotein that accumulates in the endoplasmatic reticulum (ER), near the cytosolic viroplasms, electron dense structures where the replication takes place 11 . Through an unknown mechanism, VP7 is also retained in the ER.…”

Section: Proteins Involved In Replication Pathogenesis and Immune Rementioning

confidence: 99%

Rotavirus Disease Mechanisms Diarrhea, Vomiting and Inflammation : How and Why

Hagbom¹

2015

Linköping University Medical Dissertations

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Rotavirus infections cause diarrhea and vomiting that can lead to severe dehydration. Despite extensive tissue damage and cell death, the inflammatory response is very limited. The focus of this thesis was to study pathophysiological mechanisms behind diarrhea and vomiting during rotavirus infection and also to investigate the mechanism behind the limited inflammatory response. An important discovery in this thesis was that rotavirus infection and the rotavirus toxin NSP4 stimulate release of the neurotransmitter serotonin from intestinal sensory enterochromaffin cells, in vitro and ex vivo. Interestingly, serotonin is known to be a mediator of both diarrhea and vomiting. Moreover, mice pups infected with rotavirus responded with central nervous system (CNS) activation in brain structures associated with vomiting, thus indicating a cross-talk between the gut and brain in rotavirus disease. Our finding that rotavirus infection activates the CNS led us to address the hypothesis that rotavirus infection not only activates the vagus nerve to stimulate vomiting, but also suppresses the inflammatory response via the cholinergic anti-inflammatory pathway, both of which are mediated by activated vagal afferent nerve signals into the brain stem. We found that mice lacking an intact vagus nerve, and mice lacking the α7 nicotine acetylcholine receptor (nAChR), being involved in cytokine suppression from macrophages, responded with a higher inflammatory response. Moreover, stimulated cytokine release from macrophages, by the rotavirus toxin NSP4, could be attenuated by nicotine, an agonist of the α7 nAChR. Thus, it seems most reasonable that the cholinergic anti-inflammatory pathway contributes to the limited inflammatory response during rotavirus infection. Moreover, rotavirus-infected mice displayed increased intestinal motility at the onset of diarrhea, which was not associated with increased intestinal permeability. The increased motility and diarrhea in infant mice could be attenuated by drugs acting on the enteric nervous system, indicating the importance and contribution of nerves in the rotavirus mediated disease. In conclusion, this thesis provides further insight into the pathophysiology of diarrhea and describe for the first time how rotavirus and host cross-talk to induce the vomiting reflex and limit inflammation. Results from these studies strongly support our hypothesis that serotonin and activation of the enteric nervous system and CNS contributes to diarrhea, vomiting and suppression of the inflammatory response in rotavirus disease

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Structural insights into the coupling of virion assembly and rotavirus replication

Cited by 204 publications

References 107 publications

Molecular Surveillance of Viral Processes Using Silicon Nitride Membranes

Molecular Surveillance of Viral Processes Using Silicon Nitride Membranes

Virus genomes and virus-host interactions in aquaculture animals

Rotavirus Disease Mechanisms Diarrhea, Vomiting and Inflammation : How and Why

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