Article

Structural insights into the coupling of virion assembly and rotavirus replication.

Rotavirus Molecular Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nature Reviews Microbiology (Impact Factor: 23.32). 01/2012; 10(3):165-77. DOI: 10.1038/nrmicro2673
Source: PubMed

ABSTRACT Viral replication is rapid and robust, but it is far from a chaotic process. Instead, successful production of infectious progeny requires that events occur in the correct place and at the correct time. Rotaviruses (segmented double-stranded RNA viruses of the Reoviridae family) seem to govern their replication through ordered disassembly and assembly of a triple-layered icosahedral capsid. In recent years, high-resolution structural data have provided unprecedented insight into these events. In this Review, we explore the current understanding of rotavirus replication and how it compares to replication of other Reoviridae family members.

1 Follower
 · 
468 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rotaviruses (RVs) replicate their segmented, double-stranded RNA genomes in tandem with early virion assembly. In this study, we sought to gain insight into the ultrastructure of RV assembly-replication intermediates (RIs) using transmission electron microscopy (EM). Specifically, we examined a replicase-competent, subcellular fraction that contains all known RV RIs. Three never-before-seen complexes were visualized in this fraction. Using in vitro reconstitution, we showed that ~15-nm doughnut-shaped proteins in strings were nonstructural protein 2 (NSP2) bound to viral RNA transcripts. Moreover, using immunoaffinity-capture EM, we revealed that ~20-nm pebble-shaped complexes contain the viral RNA polymerase (VP1) and RNA capping enzyme (VP3). Finally, using a gel purification method, we demonstrated that ~30–70-nm electron-dense, particle-shaped complexes represent replicase-competent core RIs, containing VP1, VP3, and NSP2 as well as capsid proteins VP2 and VP6. The results of this study raise new questions about the interactions among viral proteins and RNA during the concerted assembly–replicase process.
    Virology 03/2015; 477. DOI:10.1016/j.virol.2015.01.003 · 3.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Translation is a complex process involving diverse cellular proteins, including the translation initiation factor eIF4E, which has been shown to be a protein that is a point for translational regulation. Viruses require components from the host cell to complete their replication cycles. Various studies show how eIF4E and its regulatory cellular proteins are manipulated during viral infections. Interestingly, viral action mechanisms in eIF4E are diverse and have an impact not only on viral protein synthesis, but also on other aspects that are important for the replication cycle, such as the proliferation of infected cells and stimulation of viral reactivation. This review shows how some viruses use eIF4E and its regulatory proteins for their own benefit in order to spread themselves.
    Viruses 02/2015; 7(2):739-750. DOI:10.3390/v7020739 · 3.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mycoreovirus 1 (MyRV1) has 11 double-stranded RNA genome segments (S1 to S11) and confers hypovirulence to the chestnut blight fungus, Cryphonectria parasitica. MyRV1 genome rearrangements are frequently generated by a multifunctional protein, p29, encoded by a positive-strand RNA virus, Cryphonectria hypovirus 1. One of its functional roles is RNA silencing suppression. Here, we explored a possible link between MyRV1 genome rearrangements and the host RNA silencing pathway using wild-type (WT) and mutant strains of both MyRV1 and the host fungus. Host strains included deletion mutants of RNA silencing components such as dicer-like (dcl) and argonaute-like (agl) genes, while virus strains included an S4 internal deletion mutant MyRV1/S4ss. Consequently, intragenic rearrangements with nearly complete duplication of the three largest segments, i.e. S1, S2 and S3, were observed even more frequently in the RNA silencing-deficient strains Δdcl2 and Δagl2 infected with MyRV1/S4ss, but not with any other viral/host strain combinations. An interesting difference was noted between genome rearrangement events in the two host strains, i.e. generation of the rearrangement required prolonged culture for Δagl2 in comparison with Δdcl2. These results suggest a role for RNA silencing that suppresses genome rearrangements of a dsRNA virus. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.
    Nucleic Acids Research 03/2015; 43(7). DOI:10.1093/nar/gkv239 · 8.81 Impact Factor