USF+Reoviridae+McPeek


 * **Family: Reoviridae**
 * Background
 * Classification & Morphology
 * Taxonomy
 * Physical and Physiochemical Properties
 * Chemistry
 * Nucleic Acid
 * Proteins
 * Lipids
 * Pathology
 * Cell Tropism
 * Associated Diseases
 * Transmission
 * Geography
 * Pathogenesis
 * Important Members
 * Orbivirus - Bluetongue virus
 * Phytoreovirus – Rice Dwarf Virus
 * Rotavirus
 * Fast Facts


 * Background**

**Reoviridae** is a family of naked, double-stranded RNA viruses that are among the most complex virus families due to their proclivity for infecting a wide variety of hosts to include: vertebrate, invertebrate, plant and fungal hosts. The first reovirus was isolated from the respiratory and enteric tracts of humans and animals, these first isolates appeared to be orphans (not associated with any disease). **“REO”** is actually an acronym that refers to “//**__r__**//espiratory //**__e__**//nteric //**__o__**//rphan”, (names by [|Albert Sabin], best known for developing an oral polio vaccine) however this name is a misnomer as there are reovirisus that do cause human disease (i.e. rotavirus).

Reoviridae was first designated as a subgroup of respiratory and enteric viruses that were linked by their distinct characteristics rather than causing a common human disease. Reoviridae has 15 genera that can be subdivided into two distinct subgroups turreted (spiked) and nonturreted (smooth) (based on viral architecture. These two subgroups can be further divided into the 15 genera (9 and 6 respectively). Each of these genera have distinct structural, biological and genetic differences which are reflected in their host ranges and pathogenesis.

Reoviridae are double stranded RNA viruses (Class III in the [|Baltimore Classification System]). A feature that is distinguishing to Class III viruses, regardless of their family association, is the ability to carry out transcription of their ds RNA segments (under appropriate conditions), within the capsid. (more info located under Life Cycle) In all of these viruses the enzymes required for endogenous transcription are part of the virion structure.
 * Classification **


 * Morphology **



Reoviridae is a family of non-enveloped (naked) viruses have large particles of about 70-80 nm diameter, which contain a dsRNA genome segemented into 10-12 fragments (each normally encoding for one protein), divided into three classes based on sizes, large (L1-3), medium (M1-3) and small (S1-4). The L, M, and S genome segments encode the viral proteins ƛ, µ, and σ respectively. ([|Source])



The mature virions are non-enveloped and their capsids, which are formed by multiple proteins, have icosahedral symmetry that are generally arranged in concentric layers. Unique among viruses, Reoviridae have an outer and an inner icosahedral capsid that surrounds an inner core containing necessary enzymes for mRNA synthesis (including RNA polymerase). Most of the non enveloped, [|icosahedral virions]have a double capsid structure in which the outer capsid (exceptions are Cypovirus & Dinovernavirus),comprised of VP4 & VP7, has an icosahedral T=13 symmetry and the inner capsid, comprised of VP6, has an icosahedral symmetry of T=2 (most commonly called T=2, but some call T=1 see below). The outer two layers have channels that connect the ‘inner core’ (innermost capsid) to the ‘outer world’ and it is through this channel that newly synthesized mRNA is extruded. The inner core of the virus contains all of the enzymatic functions of the virus and has a T=1 morphology that is created by the dimers of VP2. ([|Source])



The family is divded into two subgroups Spinareovirinae and Sedorevirinae based on morphology (turreted & nonturreted). Spinareovirnae is the named used for the subfamily that contains the turreted or spiked viruses (‘spina’ Latin prefix meaning spike). Sedoreovirinae is the name used for the nonturreted viruses (‘sedo’ Latin prefix meaning smooth) as these viruses have the absence of the spikes/turrets and thus have a relatively smooth morphology. ([|Source])


 * Taxonomy **

**//Subfamily://** Sedoreovirinae **//(6 Genera)//** **//Subfamily://** Spinareovirinae **//(9 Genera)//**
 * Family: Reoviridae (2 Subfamilies) **
 * Genus: Cardoreovirus (1 Species)
 * Genus: Mimoreovirus (1 Species)
 * Genus: Orbivirus (22 Species)
 * Genus: Phytoreovirus (3 Species)
 * Genus: Rotavirus (5 Species)
 * Genus: Seadornavirus (3 Species)
 * Genus: Aquareovirus (7 Species)
 * Genus: Coltivirus (2 Species)
 * Genus: Cypovirus (16 Species)
 * Genus: Dinovernavirus (1 Species)
 * Genus: Fijivirus(8 Species)
 * Genus: Idnoreovirus (5 Species)
 * Genus: Mycoreovirus (3 Species)
 * Genus: Orthoreovirus (5 Species)
 * Genus: Oryzavirus (2 Species)

( [|Source] )


 * Physical and Physiochemical Properties **
 * Buoyant density in CsCl: 1.26 to 1.44 g cm-3
 * Resistant to these treatments:
 * Freezing
 * Carbon tetrachloride

( [|Source] )


 * Chemistry **
 * Nucleic Acid **
 * Constitutes 15 to 20 % of the virion by weight
 * Genome is monomeric
 * Genome is segmented (with all segments enclosed in a single particle)
 * Consists of or ten segments of to twelve segments of linear double-stranded RNA
 * grouped into three categories by size: L (large), M (medium) and S (small).
 * Segments size range from 0.2 to 3.0 kb
 * each segment encodes 1-3 proteins.
 * The complete genome is 18,200 to 30,500 nucleotides (18.2 to 30.5 kb.)
 * The 5' end of the genome has a cap
 * Cap is a methylated nucleotide cap on the positive strand of each duplex, the negative strands have a phosphorylated terminus
 * In capsid, the segments are hydrogen bonded to one another end-to-end
 * The 3’ end of the genome encodes translation enhancers and is not polyadenylated
 * Each virion contains a single copy of the genome
 * The genome is infectious.
 * GenBank records for complete genome sequences

( [|source] )

Proteins constitute about 80 to 85 % of the particle weight. The viral genome encodes structural proteins and non-structural proteins. Reoviridae proteins are denoted by the Greek character corresponding to the segment it was translated from (the L segment encodes for λ proteins, the M segment encodes for μ proteins and the S segment encodes for σ proteins).
 * Proteins **

( [|Source] )


 * Lipids **
 * Are usually absent
 * Can be present during morphogenesis in extremely small amounts
 * Usually as myristic acid residues that is covalently attached to 1 of the virion proteins
 * Located in the envelope in an intermediate stage that is later removed

( [|Source] )

**Life Cycle of Reoviridae from Microbiology Bytes** Virus attaches to host receptors and is endocytosed into vesicles in the host cell. The receptor(s) are known to contain sialic acid (haemagglutination, broad cell tropism), but most have not been definitively identified. However recent research indicates that Reoviridae bind to host cell surface carbohydrates and immnoglobulin superfamily member junctional adhesion molecule-A (JAM-A). The Reovirus attachment protein σ1 disrupts the JAM-A dimer, engaging a single JAM-A molecule by virtually the same interface used for JAM-A [|homodimerization] ([|Source])
 * Life Cycle – Reoviridae **
 * They are dsRNA viruses which replicate in the cytoplasm, indicating they have everything they need for replication and do not utilize the cell's replication enzymes.** Several differences exist in the modes of entry into and exit from cells between the different genera in the Reoviridae family. The most extensively studied virus of the Reoviridae family are the Orthreoviruses which enter the cell either by receptor mediated endocytosis or as a result of digestion with chymotrypsin in the intestine. Intermediate subviral particles may pass into the cytoplasm by the endosmal pathway or directly.
 * Replication cycle of the viruses in host**
 * Adsorption:**


 * Penetration & Uncoating -** Particles are internalized partially uncoated (cathepsin proteases ) in endolysosomes and penetrate in the cytoplasm. They do not fully uncoat during the process of replication because the coat is resistant to protease digestion, preventing them from being completely destroyed by the infected cell.


 * Replication (Transciption & Translation) -** Early transcription of the dsRNA genome by viral polymerase occurs inside this sub-viral particle (naked core), so that dsRNA is never exposed to the cytoplasm. Full-length plus-strand transcripts from each of the dsRNA segments are synthesized. These plus-strand transcripts are used as templates for translation. The mRNA used in translation is synthesized from the negative strand of the dsRNA. Each negative strand produces many positive strands. Particle-associated transcriptase is involved in the process. Neither of the strands of dsRNA appear among the transcription products, and both strands remain in the uncoated core particle. The capped positive strand of RNA found in progeny dsRNA is synthesized from the negative strand template found in the dsRNA within the parental cores. These capped transcripts that result from primary transcription are not polyadenylated. Secondary transcription occurs in the later stage of infection and results in uncapped non-polyadenylated transcripts. mRNAs leave the core and get translated in the cytoplasm.
 * Encapsidation -** (+)RNAs are encapsidated in a sub-viral particle, inside which they are transcribed to give RNA (-) molecules with which they become base-paired to produce dsRNA genomes.


 * Virion Assembly -** The capsid is assembled on the sub-viral particle. Viral particles begin to assemble in the cytoplasm 6–7 hours after infection.

( [|Source] )
 * Release -** Mature virions are released presumably following cell death and associated breakdown of host plasma membrane.

This family is ubiquitous in nature as it has been found to infect mammals, birds, reptiles, amphibians, fish, invertebrates, plants and fungi. Infections have been found in all species of mammals tested (except whales), which implies a wide cell tropism or a ubiquitous receptor.
 * Hosts **


 * Pathology **
 * Cell Tropism **
 * **Vertebrate –** mucosal gut cells
 * **Insect** **–** midgut cells
 * **Plants** **–** ploem neoplastic tissues
 * **Funi -** Mycelium


 * Associated Diseases****:** Vertebrate – respiratory tract disease, gastroenteritis, myalgia


 * Transmission **
 * **Vertebrate** – fecal-oral route
 * **Insects** – fecal-oral route
 * **Plants** – vectors


 * Geography** **-** Worldwide

As pathogenesis varies so greatly within Reoviridae due to its wide host range further information can be found under the important member section.
 * Pathogenesis **

( [|Source] )


 * Important Members **
 * Orbivirus** **- [|Bluetongue virus] **
 * //Orbivirus//**
 * Members contain 11 genome segments
 * Resist inactivation at pH6-7, but can be inactivated at values outside this range
 * Can be inactivated by trypsin and pepsin
 * Vector transmission by variety of arthropods (mosquitoes, sandflies, ticks)
 * Representative viruses
 * Colorado Tick Fever
 * Bluetonge Virus (affects sheep, goats and cattle)
 * African horse sickness virus
 * Epizootic hemorrhagic disease of deer


 * //[|Bluetongue Virus]//**
 * Non contagious
 * Vector transmission by insects
 * Affects domestic and wild animals
 * Affects the US more than other countries
 * Threat of decreased trade because of the outbreak is more dangerous to the industry than the actual disease
 * Can cross react with other antigentically related such as:
 * Palyam Virus
 * Epizootic Hemorrhagic Disease of Deer
 * African Horse Sickness
 * Virus can replicate in both the insect vectors and the mammalian host
 * Clinically manifests as two syndromes
 * Vascular insult o fseveral organ systems
 * Reproductive syndrom

([|Source])


 * Phytoreovirus** **– [|Rice Dwarf Virus] **
 * //Phytoreoviruses//**
 * Unique in Reoviridae, have 12 segments in each
 * Contain their own RNA-dependent RNA polymerase
 * Three recognized viruses
 * Wound Tumor Virus (WTV)
 * Rice Dwarf Virus (RDV)
 * Rice gall dwarf virus (RGDV)
 * //[|Rice Dwarf Virus]//**
 * Primarily a plant pathogen
 * Transmitted by leafhoppers (main vector of //Nephotettix cincticeps//)
 * Virus transmitted to the progeny of the vector;
 * Is not transmitted by mechanical inoculation;
 * Is not transmitted by contact between plants;
 * Is not transmitted by seed;
 * Is not transmitted by pollen.
 * Infects rice, wheat and other //graminae//
 * Causes chlorotic flecks at site of infection and stunts the plant bodies
 * One of the most economically damaging viruses in Japan and China

([|Source])


 * Rotavirus -** **[|Rotavirus]**
 * Virus causes gastroenteritis
 * Severe watery diarrhea
 * Often with vomiting, fever and abdominal pain
 * In young children can lead to dehydration
 * Is the leading cause of diarrhea in infants and young children world wide
 * In the US, prior to 2006 vaccine (see link to Standford Lecture below), virus was responsible for:
 * >200,000 ER visits
 * 55,000-70,000 hospitalizations
 * 20-60 deaths of children younger than 5
 * Members contain 11 segments
 * Resist inactivation by low and high pH and digestive enzymes
 * VP4 & VP7 are protective immunogens

media type="youtube" key="iNWbglpQPY4?version=3" height="360" width="640"
 * [|Youtube Video:] [|The New Rotavirus Vaccine: The Second Time is the Charm] **

([|Source])


 * Other Viruses of Interest**
 * //Aquareovirus//** – Host: Aquatic vertebrates and invertebrates (fish, shellfish, and crustacean species)


 * //Cypovirus//** – Host: insects


 * //Mycoreovirus//** - Host: Fungi


 * Fast Facts **


 * **What does ‘reo’ stand for in Reoviridae?** || __R__espiratory and __e__nteric __o__rphan viruses ||
 * **What type of nucleic acid does Reoviridae contain in their genome?** || Double-stranded ribonucleic acid (dsRNA) with 10-12 segments ||
 * **What is their capsid geometry** || Icoshedral ||
 * **Do they contain an envelop** || No, they are nonenveloped or ‘naked’ ||
 * **Where do they replicate** || Cytoplasm ||
 * **What enzyme is needed to aid in the replication of the rotavirus genome?** || Virus encoded RNA-dependent RNA polymerase ||
 * **What viral proteins are found in the outer coat?** || Viral protein (VP) 4, 6, 7 & integrins VP4 is cleaved to form VP5 and VP8 which are important for cell adhesion ||
 * **How are newly synthesized virions released** || By cell lyse ||
 * **How does this affect the structure of the virus** || Virions lack envelops because they are released from cells by lysis, unlike enveloped viruses that acquire their envelopes due to cell budding ||
 * **What is the transmission of reoviridae viruses?** || Vertebrate: fecal-oral route Insects: fecal-oral route Plants: Vectors - insects ||
 * **Rotavirus is the most human clinically significant virus of Reoviridae, what does is cause?** || Gastroenteritis in infants and young children? ||
 * **What is the cell tropism for Reoviridae** || Vertebrate: mucosal gut cells Insect: midgut cells Plants: phloem neoplastic tissues ||
 * **What viral proteins are found in the outer coat?** || Viral protein (VP) 4, 6, 7 & integrins VP4 is cleaved to form VP5 and VP8 which are important for cell adhesion ||
 * **How are newly synthesized virions released** || By cell lyse ||
 * **How does this affect the structure of the virus** || Virions lack envelops because they are released from cells by lysis, unlike enveloped viruses that acquire their envelopes due to cell budding ||
 * **What is the transmission of reoviridae viruses?** || Vertebrate: fecal-oral route Insects: fecal-oral route Plants: Vectors - insects ||
 * **Rotavirus is the most human clinically significant virus of Reoviridae, what does is cause?** || Gastroenteritis in infants and young children? ||
 * **What is the cell tropism for Reoviridae** || Vertebrate: mucosal gut cells Insect: midgut cells Plants: phloem neoplastic tissues ||
 * **What is the transmission of reoviridae viruses?** || Vertebrate: fecal-oral route Insects: fecal-oral route Plants: Vectors - insects ||
 * **Rotavirus is the most human clinically significant virus of Reoviridae, what does is cause?** || Gastroenteritis in infants and young children? ||
 * **What is the cell tropism for Reoviridae** || Vertebrate: mucosal gut cells Insect: midgut cells Plants: phloem neoplastic tissues ||
 * **What is the cell tropism for Reoviridae** || Vertebrate: mucosal gut cells Insect: midgut cells Plants: phloem neoplastic tissues ||
 * **What is the cell tropism for Reoviridae** || Vertebrate: mucosal gut cells Insect: midgut cells Plants: phloem neoplastic tissues ||

([|Source])