In the name of Allah The compassionate the merciful

REOVIRUS reo: respiratory enteric orphan, early recognition that the viruses caused respiratory and enteric infections incorrect belief they were not associated with disease, hence they we re considered "orphan " viruses

VIRION Naked icosahedral capsid (T=13), Diameter 60–85 nm. Naked icosahedral capsid (T=13), Diameter 60–85 nm. Capsid consists of two or three concentricprotein shells. Capsid consists of two or three concentricprotein shells. Inner capsid (T=1), or core, contains RNA polymerase and capping enzymes. Inner capsid (T=1), or core, contains RNA polymerase and capping enzymes. Linear double-stranded RNA, 10–12 segments. Total genome length 18–24 kb. Linear double-stranded RNA, 10–12 segments. Total genome length 18–24 kb. infect invertebrates, vertebrates and plants, infect invertebrates, vertebrates and plants,

structure

Reoviruses were the first double-stranded RNA viruses discovered. First recognized isolated from stool specimens the 1950s by Albert Sabin, Leon Rosen and their colleagues. First recognized isolated from stool specimens the 1950s by Albert Sabin, Leon Rosen and their colleagues. In the early 1960s, Peter Gomatos and Igor Tamm. the viral genome consists of double- stranded RNA. In the early 1960s, Peter Gomatos and Igor Tamm. the viral genome consists of double- stranded RNA. The Reoviridae family presently includes 12 genera The Reoviridae family presently includes 12 genera The mammalian reoviruses are the type species of the Orthoreovirus The mammalian reoviruses are the type species of the Orthoreovirus

GenusSegmentsHostVector Orthoreovirus10MammalsNone Orbivirus11MammalsMosquitoes, flies Rotavirus11MammalsNone Coltivirus12MammalsTicks Seadornavirus12MammalsTicks Aquareovirus11FishNone Hypexreovirus10MammalsNone Cypovirus10InsectNone Fijivirus10PlantPlanthopper Phytoreovirus12PlantLeafhopper Oryzavirus10PlantPlanthopper Mycoreovirus11 or 12FungiNone Family Reoviridae

Other recognized genera of Reoviridae that infect animalhosts are Rotavirus, Orbivirus, Coltivirus, and Aquareovirus Other recognized genera of Reoviridae that infect animalhosts are Rotavirus, Orbivirus, Coltivirus, and Aquareovirus orbivirus can cause bluetongueof sheep and cow orbivirus can cause bluetongueof sheep and cow Coltiviruses can cause Colorado tick fever. Coltiviruses can cause Colorado tick fever. Rotaviruses are responsible for gastroenteritis in animals and humans Rotaviruses are responsible for gastroenteritis in animals and humans

Genus: Rotavirus Type species: Human Rotavirus Type species: Human Rotavirus 11 segments of ds RNA 11 segments of ds RNA rota: from Latin rota, "wheel " rota: from Latin rota, "wheel " Mammals Mammals

Some times called DUO viruses

Reovirus gene segments range 1200 to 3900 bp Reovirus gene segments range 1200 to 3900 bp classified as large (L), medium (M), or small (S) in polyacrylamide gels classified as large (L), medium (M), or small (S) in polyacrylamide gels Nine of the 10 segments code for asingle protein the exception is the S1 gene, Nine of the 10 segments code for asingle protein the exception is the S1 gene, L ‑ encodes proteins designated lambda ~3.9kbp L ‑ encodes proteins designated lambda ~3.9kbp M ‑ encodes proteins designated mu M ‑ encodes proteins designated mu S ‑ encodes proteins designated sigma ‑ 1kbp S ‑ encodes proteins designated sigma ‑ 1kbp Genome

Reoviruses contain exactly one segment of each of the segments of dsRNA that constitute the viral genome, encapsidated in a single complex virus particle comprised of 6-8 proteins

Nontranslated from 12–32 nt to 32–83 nt Nucleotide sequence conservation inward both nontranslated regions

The attachment protein binds to one or two cellular receptors attachment protein sigma 1 is a long, fi berlike molecule with head-and-tail morphology. two receptor-binding domains: one in the tail, which binds to sialic acid, and another in the head, which binds to junctional adhesion molecule A (JAM-A)

attachment Receptor(s) contain sialic acid not definitively identified. Penetration Particles are internalized & partially uncoated in endolysosomes in the cytoplasm resistant to protease digestion ‑ if completely uncoated, virus destroyedattachment Receptor(s) contain sialic acid not definitively identified. Penetration Particles are internalized & partially uncoated in endolysosomes in the cytoplasm resistant to protease digestion ‑ if completely uncoated, virus destroyed

virions undergo partial degradation by cellular proteases, resulting in the generation of infectious subvirion particles (ISVPs).

transcription transcription Early transcription Early transcription d/s RNA genome d/s RNA genome viral polymerase viral polymerase inside this sub ‑ viral particle. inside this sub ‑ viral particle. various genome segments are transcribed/translated at different frequencies various genome segments are transcribed/translated at different frequencies Replication:

RNA is transcribed conservatively ‑ RNA is transcribed conservatively ‑ only ( ‑ )sense strands are used, only ( ‑ )sense strands are used, resulting in synthesis of (+)sense mRNAs, resulting in synthesis of (+)sense mRNAs, capped inside the core ‑ capped inside the core ‑ not polyadenylated not polyadenylated without de novo protein synthesis. without de novo protein synthesis. Secondary transcription Secondary transcription later later in particles produced inside the infected cells and results in uncapped non-polyadenylated transcripts. in particles produced inside the infected cells and results in uncapped non-polyadenylated transcripts. mRNAs leave core & are translated in the cytoplasm. mRNAs leave core & are translated in the cytoplasm. 5 enzymatic activities are present in reovirus particles to carry out this process 5 enzymatic activities are present in reovirus particles to carry out this process not necessarily all separate peptides not necessarily all separate peptidesReplication:

It results in production of capped transcripts that serve both as mRNAs for translation and as templates for [+]-strand synthesis within progeny particles. Primary transcripts are detected by 2 hours after infection, reach a maximum at 6 to 8 hours, It results in production of capped transcripts that serve both as mRNAs for translation and as templates for [+]-strand synthesis within progeny particles. Primary transcripts are detected by 2 hours after infection, reach a maximum at 6 to 8 hours, Primary Transcription in Cells

Capped, methylated mRNAs are transcribed by reovirus core particles

RNA replication genome is replicated in the cytoplasm in a conservative fashion excess of (+)sense strands are produced serve as late mRNA template for ( ‑ )sense strand synthesis each ( ‑ ) strand leads to many (+) strands ‑ not one ‑ for ‑ one as semi ‑ conservative replication RNA polymerase complex, composed of one molecule of 3 and one or two mµµolecules of µ 2, is located at the base of each of the lambda 2 spikes.

Secondary transcription is defined as that mediated by newly assembled subviral particles in infected cells. These particles must be derived from those with replicase activity, and they appear to be distinguishable by sedimentation behavior, by the presence of a full complement of dsRNA, by the presence of variable amounts of protein µNS, and by reduced amounts of λ2 and the other outer-capsid proteins. Secondary transcription is defined as that mediated by newly assembled subviral particles in infected cells. These particles must be derived from those with replicase activity, and they appear to be distinguishable by sedimentation behavior, by the presence of a full complement of dsRNA, by the presence of variable amounts of protein µNS, and by reduced amounts of λ2 and the other outer-capsid proteins. Secondary Transcription

Reovirus: dsRNA Virus Strategy Subviral particles in cytoplasm are sites of RNA synthesis Proteolysis during entry through lysosome activates RNA synthesis Extruded into cytoplasm through channels in 5-fold axes Remain in cytoplasm: translated Packaged into new subviral particles: templates for –RNA synthesis to produce new dsRNAs ‘core’ Capped ss(+) RNA [mRNAs] synthesized [10 dsRNA genome segments] RdRP:  1 packaged in virion

assembly assembly mechanism responsible for segregation of the various genome segments into developing particles is not known. mechanism responsible for segregation of the various genome segments into developing particles is not known. Particles assemble in the cytoplasm 6 ‑ 7h after infection ‑ inclusion bodies. Particles assemble in the cytoplasm 6 ‑ 7h after infection ‑ inclusion bodies. RELEASE RELEASE Rotaviruses bud from the E.R. into internal spaces Rotaviruses bud from the E.R. into internal spaces released when the the cell lyses. released when the the cell lyses.

assembly

Assortment of gene segments and virion assembly

Effects on Host Cells Outcomes of Infection Induction of Apoptosis ( NF-kB and IRF-3) Inhibition of Cellular DNA Synthesis and Cell-cycle Progression Induction of Apoptosis ( NF-kB and IRF-3) Inhibition of Cellular DNA Synthesis and Cell-cycle Progression Interferon by induction of double-stranded RNA-dependent protein kinase R (PKR) and ribonuclease L Effects on Virus Replication Interferon by induction of double-stranded RNA-dependent protein kinase R (PKR) and ribonuclease L Effects on Virus Replication Effects on Cellular RNA and Protein Synthesis Effects on Cellular RNA and Protein Synthesis

PKR regulation and cancer. Activated signaling pathwayssuch as the Ras pathway interfere with PKR function intransformed cells

Studies of reovirus pathogenesis in mice type 1:infect ependymalcells, leading to nonlethal hydrocephalus. type 1:infect ependymalcells, leading to nonlethal hydrocephalus. type 3:cause a fatal encephalitis. type 3:cause a fatal encephalitis. myocarditis myocarditis jaundice jaundice