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Spotlight

Articles of Significant Interest Selected from This Issue by the Editors

DOI: 10.1128/JVI.00101-17
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Reovirus Induces Necroptosis

Death of host cells following mammalian reovirus infection is a determinant of viral disease. Berger et al. (e02404-16) report that infection of some cell types by reovirus results in cell death via RIP3 kinase-dependent necroptosis. Necroptosis following reovirus infection requires the detection of genomic RNA within incoming virions to produce type I inteferons. Furthermore, de novo synthesis of viral double-stranded RNA within infected cells also is required for the induction of necroptosis. In addition to describing a new pathway for reovirus-induced cell death, this work highlights a link between innate recognition of RNA viruses and necroptotic cell death.

Figure1
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Model for reovirus-induced necroptosis.

Efficient Deep-Sequencing Quantification of HIV-1 Splicing

Alternate splicing of HIV-1 transcripts produces over 50 conserved RNAs that can be quantified using a new assay that combines transcript deep sequencing with Primer ID template indexing. Emery et al. (e02515-16) developed an assay to quantify temperature- and structure-dependent splicing changes and compare splicing among viral strains. Differences in the two transcript size classes (4 kb and 1.8 kb) suggest that Rev-dependent transcripts experience a different splicing environment than that for completely spliced transcripts. The relative ease of this three-primer assay paired with the capacity of next-generation sequencing provide a new tool for studying the regulation of the HIV-1 splicing program.

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Splicing in 4-kb and 1.8-kb mRNAs.

New Insights into Baculovirus Nucleocapsid Assembly

The baculovirus vp39 gene encodes a major nucleocapsid protein, but many critical domains and residues of the VP39 protein product have not been identified. Katsuma and Kokusho (e02253-16) report the isolation of a vp39 mutant and identify Gly-276 as a conserved residue essential to the function of VP39 in nucleocapsid assembly. This work also provides evidence for a link between nucleocapsid formation and transcription of the baculovirus polyhedrin and p10 very late genes.

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Large and aberrant nucleocapsid-like structures produced by a vp39-mutated baculovirus.

Chikungunya, Influenza, Nipah, and Semliki Forest Chimeric Viruses with Vesicular Stomatitis Virus: Actions in the Brain

Vesicular stomatitis virus (VSV) shows promise as a vaccine vehicle and an oncolytic agent. However, VSV-G glycoprotein targets neurons, which can generate adverse effects in the brain. van den Pol et al. (e02154-16) compare chimeric viruses expressing combinations of VSV genes together with genes from chikungunya, influenza, Nipah, or Semliki Forest viruses. A chimeric chikungunya virus-VSV appeared safe in the rodent brain. In contrast, Nipah F+G-VSV was more lethal than wild-type VSV. These results suggest that while chimeric VSVs show promise, each must be tested for neural injury.

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VSVΔG-NipahF+G infects neurons in brain.

Increased Matrix Metalloproteinase Activity Associated with Mouse Adenovirus-Induced Encephalitis

Blood-brain barrier (BBB) disruption can accompany viral encephalitis, and matrix metalloproteinases (MMPs) degrade BBB components. Ashley et al. (e01412-16) discovered that mouse adenovirus type 1 (MAV-1) induces MMP activity in susceptible mouse brains. Astrocytes and microglia infected ex vivo secrete activated MMPs and may directly contribute to BBB breakdown. Conditioned medium from these cells also induces MMP activity from MAV-1-infected endothelial cells, suggesting an indirect mechanism of BBB disruption in encephalitic virus infections.

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MAV-1 infects GFAP+ astrocytes and IBA1+ microglia.

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Articles of Significant Interest Selected from This Issue by the Editors
Journal of Virology Feb 2017, 91 (6) e00101-17; DOI: 10.1128/JVI.00101-17

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Articles of Significant Interest Selected from This Issue by the Editors
Journal of Virology Feb 2017, 91 (6) e00101-17; DOI: 10.1128/JVI.00101-17
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  • Article
    • Reovirus Induces Necroptosis
    • Efficient Deep-Sequencing Quantification of HIV-1 Splicing
    • New Insights into Baculovirus Nucleocapsid Assembly
    • Chikungunya, Influenza, Nipah, and Semliki Forest Chimeric Viruses with Vesicular Stomatitis Virus: Actions in the Brain
    • Increased Matrix Metalloproteinase Activity Associated with Mouse Adenovirus-Induced Encephalitis
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