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. Inner capsid, or core, contains RNA polymerase and capping enzymes.

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

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.

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.

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.

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.

Virion Reoviruses were the first double-stranded 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 Messenger RNA synthesis. l3, m 2 at l2 spikes Messenger RNA capping. l2 spike protein Messenger RNA export. Fig. 24.6 Synthesis of reovirus messenger RNAs.

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

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

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.

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 CDK by s1s

Key Terms Jaundice Adherens junction 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 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