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Reoviruses - Reoviridae

Reoviruses - Reoviridae. Virion. Genome. Genes and proteins. Viruses and hosts. Diseases. Distinctive characteristics. Reoviruses - Reoviridae. Virion Naked icosahedral capsid Diameter 60–85 nm. Capsid consists of two or three concentric protein shells.

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Reoviruses - Reoviridae

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  1. Reoviruses - Reoviridae Virion Genome Genes and proteins Viruses and hosts Diseases Distinctive characteristics

  2. Reoviruses - Reoviridae • Virion • Naked icosahedral capsid • Diameter 60–85 nm. • Capsid consists of two or three concentric protein shells. • Inner capsid, or core, contains RNA polymerase and capping enzymes.

  3. Reoviruses - Reoviridae • Genome • Linear ds RNA. • 10–12 segments. • Total genome length 18–24 Kb.

  4. Reoviruses - Reoviridae • Genes and proteins • mRNAs are full-length copies of each genome segment. • Typically one protein encoded per genome segment. • Six–eight capsid proteins. • Three–six nonstructural proteins.

  5. Reoviruses - Reoviridae • Viruses and hosts • Twelve genera, including Orthoreovirus, Rotavirus, Orbivirus. • Infect humans (reoviruses types I–III, rotaviruses, Colorado tick fever virus), mammals, birds, fish, mollusks, plants, insects, and fungi.

  6. Reoviruses - Reoviridae • Diseases • Members of genus Orthoreovirus cause little or no disease in humans. • Rotavirus gastroenteritis is an important cause of infant disease in the developed world and • infant mortality in the developing world. • Viruses spread between hosts by direct transmission, contaminated food or water, or arthropod vectors.

  7. Reoviruses - Reoviridae • Distinctive characteristics • Family has members that infect a broad range of hosts from fungi to humans. • mRNAs are synthesized and capped inside intact cores and extruded through channels into the cytosol. • Synthesis of double-stranded genome RNAs occurs within core-like subvirion particles. • A single copy of each gene segment is packaged into each virion by an unknown sorting mechanism. • Gene segments can be reassorted during coinfection of cells by different strains.

  8. Virion • Reoviruses were the first double-stranded RNA viruses discovered

  9. Virion • Reoviridae have segmented genomes made of double-stranded RNA Fig. 24.1 The reovirus virion.

  10. Virion • Reoviridae have segmented genomes made of double-stranded RNA Fig. 24.2 Generation of reassortant viruses.

  11. Genome Fig. 24.3 Features of reovirus gene segments.

  12. Genes and proteins • Reovirus virions contain concentric layers of capsid proteins

  13. Genes and proteins • The attachment protein binds to one or two cellular receptors

  14. Genes and proteins • The attachment protein binds to one or two cellular receptors • from virions and the core is released into the cytoplasm Fig. 24.4 Stepwise disassembly of reovirus.

  15. Genes and proteins • Enzymes in the viral core synthesize and cap messenger RNAs • Messenger RNA synthesis. • l3, m 2at l2 spikes • Messenger RNA capping. • l2 spike protein • Messenger RNA export. Fig. 24.6 Synthesis of reovirus messenger RNAs.

  16. Genes and proteins • Translation of reovirus mRNAs is regulated • Not all reo virus proteins are produced in the same amount • The length of mRMA • Sequences around AUG • Difference in the length of 5’ UTR • NSP3 binds 3’ end of mRNA and also 5’ cap complex • functionally replace PABP for efficient translation

  17. Genes and proteins • Interferon and PKR: effects on viral and cellular protein synthesis • The s3 protein modulates PKR activation. • Binds to ds RNA, competing with PKR • PKR regulation and cancer. • Replicates more efficiently in transformed cells • Acitivated Ras signal interferes with PKR function • Might be useful as novel oncolytic agents

  18. Genes and proteins • Synthesis of progeny double-stranded genomes occurs within subviral particles • Virus factories. • Intracytoplasmic inclusions • Replicase particles. • Secondary transcription and encapsidation. Fig. 24.8 Assortment of gene segments and virion assembly.

  19. Genes and proteins • Reoviruses induce apoptosis via activation of transcription factor NF-B • Receptor binding and apoptosis. • Binding to sialic acid and JAM-A is required for maximal levels of apoptosis • Cell-cycle arrest. • Arrest G2/M transition • Due to hyperphosphorylation and activation of CDKby s1s

  20. Adherens junction Apoptosis Caspases Cathepsins Cryoelectron microscopy Cyclin-dependent kinase (CDK) Double-stranded RNA-dependent protein kinase (PKR) Encephalitis Ependymal cells Hydrocephalus Inclusion bodies Infectious subvirion particles (ISVPs) Interferons Jaundice Junctional adhesion molecule A (JAM-A) Myocarditis Nectins NF-kB (nuclear factor-kB) 2’, 5’-oligo(A) synthetase Oncolytic Ras Reassortant viruses Ribonuclease L Sialic acid Tight junction Tropism Key Terms

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