| Double-stranded RNA viruses | |
|---|---|
 | |
| Electron micrograph ofrotaviruses. The bar = 100 nm | |
| Virus classification | |
| Group: | Group III(dsRNA) |
| Kingdom: Phylum: Class | |
Double-stranded RNA viruses (dsRNA viruses) are apolyphyletic group ofviruses that havedouble-stranded genomes made ofribonucleic acid. The double-stranded genome is used as a template by the viralRNA dependent RNA polymerase (RdRp) totranscribe apositive-strand RNA functioning asmessenger RNA (mRNA) for thehost cell'sribosomes, whichtranslate it into viral proteins. The positive-strand RNA can also be replicated by the RdRp to create a new double-stranded viral genome.[1]
A distinguishing feature of the dsRNA viruses is their ability to carry out transcription of the dsRNA segments within thecapsid, and the requiredenzymes are part of the virion structure.[2]
Double-stranded RNA viruses are classified into two phyla,Duplornaviricota andPisuviricota (specifically classDuplopiviricetes), in the kingdomOrthornavirae andrealmRiboviria. The two phyla do not share a common dsRNA virus ancestor, but evolved their double strands two separate times frompositive-strand RNA viruses. In theBaltimore classification system, dsRNA viruses belong to Group III.[3]
Virus group members vary widely in host range (animals,plants,fungi, andbacteria), genome segment number (one to twelve), andvirion organization (T-number,capsid layers, or turrets). Double-stranded RNA viruses include therotaviruses, known globally as a common cause ofgastroenteritis in young children, andbluetongue virus, an economically significant pathogen of cattle and sheep. The familyReoviridae is the largest and most diverse dsRNA virus family in terms of host range.[2]
Two clades of dsRNA viruses exist: the phylumDuplornaviricota and the classDuplopiviricetes, which is in the phylumPisuviricota. Both are included in the kingdomOrthornavirae in the realmRiboviria. Based on phylogenetic analysis of RdRp, the two clades do not share a common dsRNA ancestor but are instead separately descended from different positive-sense, single-stranded RNA viruses. In theBaltimore classification system, which groups viruses together based on their manner of mRNA synthesis, dsRNA viruses are group III.[3][4]
Duplornaviricota contains most dsRNA viruses, includingreoviruses, which infect a diverse range of eukaryotes, andcystoviruses, which are the only dsRNA viruses known to infect prokaryotes. Apart from RdRp, viruses inDuplornaviricota also share icosahedral capsids that contain 60 homo- or heterodimers of the capsid protein organized on a pseudo T=2 lattice. The phylum is divided into three classes:Chrymotiviricetes, which primarily contains fungal and protozoan viruses,Resentoviricetes, which contains reoviruses, andVidaverviricetes, which contains cystoviruses.[3][4]
The classDuplopiviricetes is the second clade of dsRNA viruses and is in the phylumPisuviricota, which also contains positive-sense single-stranded RNA viruses.Duplopiviricetes mostly contains plant and fungal viruses and includes the following four families:Amalgaviridae,Hypoviridae,Partitiviridae, andPicobirnaviridae.[3][4]
Reoviridae are currently classified into ninegenera. The genomes of these viruses consist of 10 to 12 segments ofdsRNA, each generally encoding oneprotein. The mature virions are non-enveloped. Their capsids, formed by multiple proteins, haveicosahedral symmetry and are arranged generally in concentric layers.
Theorthoreoviruses (reoviruses) are the prototypic members of the virusReoviridae family and representative of the turreted members, which comprise about half the genera. Like other members of the family, the reoviruses are non-enveloped and characterized by concentric capsid shells that encapsidate a segmented dsRNAgenome. In particular, reovirus has eight structural proteins and ten segments of dsRNA. A series of uncoating steps and conformational changes accompany cell entry and replication. High-resolution structures are known for almost all of the proteins of mammalian reovirus (MRV), which is the best-studied genotype. Electron cryo-microscopy (cryoEM) and X-raycrystallography have provided a wealth of structural information about two specific MRV strains, type 1 Lang (T1L) and type 3 Dearing (T3D).[5]
The cytoplasmic polyhedrosis viruses (CPVs) form the genusCypovirus of the familyReoviridae. CPVs are classified into 14 species based on theelectrophoretic migration profiles of their genome segments. Cypovirus has only a single capsid shell, which is similar to the orthoreovirus inner core. CPV exhibits striking capsid stability and is fully capable of endogenous RNA transcription and processing. The overall folds of CPV proteins are similar to those of other reoviruses. However, CPV proteins have insertional domains and unique structures that contribute to their extensive intermolecular interactions. The CPV turret protein contains twomethylase domains with a highly conservedhelix-pair/β-sheet/helix-pair sandwich fold but lacks the β-barrel flap present in orthoreovirusλ2. The stacking of turret protein functional domains and the presence of constrictions and A spikes along the mRNA release pathway indicate a mechanism that uses pores and channels to regulate the highly coordinated steps of RNA transcription, processing, and release.[6]
Rotavirus is the most common cause of acutegastroenteritis in infants and young children worldwide. This virus contains a dsRNA genome and is a member of theReoviridae family. The genome of rotavirus consists of eleven segments of dsRNA. Each genome segment codes for one protein with the exception of segment 11, which codes for two proteins. Among the twelve proteins, six are structural and six are non-structural proteins.[7]It is a double-stranded RNA non-enveloped virus. When at least tworotavirus genomes are present in a host cell, the genome segments may undergo reassortment to form progeny viruses with new gene combinations,[8] or they may undergo intragenic homologous recombination.[9] Some pathogenic rotavirus lineages that infect humans appear to have evolved through multiple interspecies reassortment events.[10] Intragenic homologous recombination also appears to be a significant driver of rotavirus diversity and evolution.[9] Intragenic recombination may occur when the VP1 RNA-dependent RNA polymerase replicates part of one template strand before switching to another.[9]
The members of genusOrbivirus within theReoviridae family arearthropod borne viruses and are responsible for high morbidity and mortality inruminants.Bluetongue virus (BTV) which causes disease in livestock (sheep,goat,cattle) has been in the forefront of molecular studies for the last three decades and now represents the best understoodorbivirus at the molecular and structural levels. BTV, like other members of the family, is a complex non-enveloped virus with seven structural proteins and a RNA genome consisting of 10 variously sized dsRNA segments.[11][12]
Phytoreoviruses are non-turretedreoviruses that are major agricultural pathogens, particularly in Asia. One member of this family,Rice Dwarf Virus (RDV), has been extensively studied byelectron cryomicroscopy andx-ray crystallography. From these analyses, atomic models of the capsid proteins and a plausible model for capsid assembly have been derived. While the structural proteins of RDV share no sequence similarity to other proteins, their folds and the overall capsid structure are similar to those of otherReoviridae.[13]
TheL-A dsRNA virus of theyeastSaccharomyces cerevisiae has a single 4.6 kb genomic segment that encodes its major coat protein, Gag (76 kDa) and a Gag-Pol fusion protein (180 kDa) formed by a -1 ribosomal frameshift. L-A can support the replication andencapsidation in separate viral particles of any of several satellite dsRNAs, called M dsRNAs, each of which encodes a secreted protein toxin (the killer toxin) and immunity to that toxin. L-A and M are transmitted from cell to cell by the cytoplasmic mixing that occurs in the process of mating. Neither is naturally released from the cell or enters cells by other mechanisms, but the high frequency of yeast mating in nature results in the wide distribution of these viruses in natural isolates. Moreover, the structural and functional similarities with dsRNA viruses of mammals has made it useful to consider these entities as viruses.[14]
Infectious bursal disease virus (IBDV) is the best-characterized member of the familyBirnaviridae. These viruses have bipartite dsRNA genomes enclosed in single layered icosahedral capsids withT = 13l geometry. IBDV shares functional strategies and structural features with many other icosahedral dsRNA viruses, except that it lacks theT = 1 (or pseudoT = 2) core common to theReoviridae,Cystoviridae, andTotiviridae. The IBDV capsid protein exhibits structural domains that show homology to those of the capsid proteins of some positive-sense single-stranded RNA viruses, such as thenodaviruses andtetraviruses, as well as theT = 13 capsid shell protein of theReoviridae. TheT = 13 shell of the IBDV capsid is formed by trimers of VP2, a protein generated by removal of the C-terminal domain from its precursor, pVP2. The trimming of pVP2 is performed on immature particles as part of the maturation process. The other major structural protein, VP3, is a multifunctional component lying under theT = 13 shell that influences the inherent structural polymorphism of pVP2. The virus-encoded RNA-dependentRNA polymerase, VP1, is incorporated into the capsid through its association with VP3. VP3 also interacts extensively with the viral dsRNA genome.[15]
Bacteriophage Φ6, is a member of theCystoviridae family. It infectsPseudomonas bacteria (typically plant-pathogenicP. syringae). It has a three-part, segmented, double-stranded RNA genome, totalling ~13.5 kb in length. Φ6 and its relatives have a lipid membrane around their nucleocapsid, a rare trait amongbacteriophages. It is a lytic phage, though under certain circumstances has been observed to display a delay in lysis which may be described as a "carrier state".[16]
Since cells do not produce double-stranded RNA during normalnucleic acid metabolism, natural selection has favored the evolution of enzymes that destroy dsRNA on contact. The best known class of this type of enzymes isDicer. It is hoped that broad-spectrum anti-virals could be synthesized that take advantage of this vulnerability of double-stranded RNA viruses.[17]
...a new broad-spectrum antiviral approach, dubbed Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO)...
