Transcript Introduction to Virology

Reoviruses - Reoviridae
Virion
Genome
Genes and proteins
Viruses and hosts
Diseases
Distinctive characteristics
Reoviruses - Reoviridae
 Virion
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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.
Reoviruses - Reoviridae
 Genome
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Linear ds RNA.
10–12 segments.
Total genome length 18–24 Kb.
Reoviruses - Reoviridae
 Genes and proteins
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mRNAs are full-length copies of each
genome segment.
Typically one protein encoded per genome
segment.
Six–eight capsid proteins.
Three–six nonstructural proteins.
Reoviruses - Reoviridae
 Viruses and hosts
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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.
Reoviruses - Reoviridae
 Diseases
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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.
Reoviruses - Reoviridae
 Distinctive characteristics
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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.
Virion
 Reoviruses
were the first
doublestranded RNA
viruses
discovered
Virion
 Reoviridae have segmented genomes made
of double-stranded RNA
Fig. 24.1 The reovirus virion.
Virion
 Reoviridae have segmented genomes made
of double-stranded RNA
Fig. 24.2 Generation of
reassortant viruses.
Genome
Fig. 24.3 Features of reovirus gene segments.
Genes and proteins
 Reovirus virions contain concentric layers of
capsid proteins
Genes and proteins
 The attachment protein binds to one or two
cellular receptors
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.
Genes and proteins
 Enzymes in the viral core synthesize and cap
messenger RNAs
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Messenger RNA synthesis.
 l3, m 2 at l2 spikes
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Messenger RNA capping.
 l2 spike protein
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Messenger RNA export.
Fig. 24.6 Synthesis of reovirus messenger RNAs.
Genes and proteins
 Translation of reovirus mRNAs is regulated
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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
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NSP3 binds 3’ end of mRNA and also 5’ cap
complex
 functionally replace PABP for efficient translation
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
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PKR regulation and cancer.
 Replicates more efficiently in transformed
cells
 Acitivated Ras signal interferes with PKR
function
 Might be useful as novel oncolytic agents
Genes and proteins
 Synthesis of progeny double-stranded
genomes occurs within subviral particles
 Virus factories.
 Intracytoplasmic inclusions
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Replicase particles.
Secondary transcription and
encapsidation.
Fig. 24.8 Assortment of gene segments and
virion assembly.
Genes and proteins
 Reoviruses induce apoptosis via activation of
transcription factor NF-B
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Receptor binding and apoptosis.
 Binding to sialic acid and JAM-A is required for maximal levels of
apoptosis
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Cell-cycle arrest.
 Arrest G2/M transition
 Due to hyperphosphorylation and activation of CDK by s1s
Key Terms
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Adherens junction
Apoptosis
Caspases
Cathepsins
Cryoelectron microscopy
Cyclin-dependent kinase (CDK)
Double-stranded RNAdependent protein kinase (PKR)
Encephalitis
Ependymal cells
Hydrocephalus
Inclusion bodies
Infectious subvirion particles
(ISVPs)
Interferons
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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