Double-stranded RNA virus | |
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Electron micrograph of rotaviruses. The bar = 100 nm | |
Virus classification | |
Group: | Group III (dsRNA) |
Kingdom: Phylum: Class | |
Double-stranded RNA viruses (dsRNA viruses) are a polyphyletic group of viruses that have double-stranded genomes made of ribonucleic acid. The double-stranded genome is used as a template by the viral RNA-dependent RNA polymerase (RdRp) to transcribe a positive-strand RNA functioning as messenger RNA (mRNA) for the host cell's ribosomes, which translate 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 the capsid, and the required enzymes are part of the virion structure. [2]
Double-stranded RNA viruses are classified into two phyla, Duplornaviricota and Pisuviricota (specifically class Duplopiviricetes ), in the kingdom Orthornavirae and realm Riboviria . The two phyla do not share a common dsRNA virus ancestor, but evolved their double strands two separate times from positive-strand RNA viruses. In the Baltimore classification system, dsRNA viruses belong to Group III. [3]
Virus group members vary widely in host range (animals, plants, fungi, and bacteria), genome segment number (one to twelve), and virion organization (T-number, capsid layers, or turrets). Double-stranded RNA viruses include the rotaviruses, known globally as a common cause of gastroenteritis in young children, and bluetongue virus, an economically significant pathogen of cattle and sheep. The family Reoviridae is the largest and most diverse dsRNA virus family in terms of host range. [2]
Two clades of dsRNA viruses exist: the phylum Duplornaviricota and the class Duplopiviricetes, which is in the phylum Pisuviricota. Both are included in the kingdom Orthornavirae in the realm Riboviria. 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 the Baltimore 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, including reoviruses, which infect a diverse range of eukaryotes, and cystoviruses, which are the only dsRNA viruses known to infect prokaryotes. Apart from RdRp, viruses in Duplornaviricota 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, and Vidaverviricetes, which contains cystoviruses. [3] [4]
The class Duplopiviricetes is the second clade of dsRNA viruses and is in the phylum Pisuviricota , 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 , and Picobirnaviridae . [3] [4]
Reoviridae are currently classified into nine genera. The genomes of these viruses consist of 10 to 12 segments of dsRNA, each generally encoding one protein. The mature virions are non-enveloped. Their capsids, formed by multiple proteins, have icosahedral symmetry and are arranged generally in concentric layers.
The orthoreoviruses (reoviruses) are the prototypic members of the virus Reoviridae 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 dsRNA genome. 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-ray crystallography 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 genus Cypovirus of the family Reoviridae . CPVs are classified into 14 species based on the electrophoretic 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 two methylase domains with a highly conserved helix-pair/β-sheet/helix-pair sandwich fold but lacks the β-barrel flap present in orthoreovirus λ2. 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 acute gastroenteritis in infants and young children worldwide. This virus contains a dsRNA genome and is a member of the Reoviridae 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.
The members of genus Orbivirus within the Reoviridae family are arthropod borne viruses and are responsible for high morbidity and mortality in ruminants. 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 understood orbivirus 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. [8] [9]
Phytoreoviruses are non-turreted reoviruses that are major agricultural pathogens, particularly in Asia. One member of this family, Rice Dwarf Virus (RDV), has been extensively studied by electron cryomicroscopy and x-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 other Reoviridae. [10]
The L-A dsRNA virus of the yeast Saccharomyces 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 and encapsidation 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. [11]
Infectious bursal disease virus (IBDV) is the best-characterized member of the family Birnaviridae. These viruses have bipartite dsRNA genomes enclosed in single layered icosahedral capsids with T = 13l geometry. IBDV shares functional strategies and structural features with many other icosahedral dsRNA viruses, except that it lacks the T = 1 (or pseudo T = 2) core common to the Reoviridae, Cystoviridae, and Totiviridae. 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 the nodaviruses and tetraviruses, as well as the T = 13 capsid shell protein of the Reoviridae. The T = 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 the T = 13 shell that influences the inherent structural polymorphism of pVP2. The virus-encoded RNA-dependent RNA polymerase, VP1, is incorporated into the capsid through its association with VP3. VP3 also interacts extensively with the viral dsRNA genome. [12]
Bacteriophage Φ6, is a member of the Cystoviridae family. It infects Pseudomonas bacteria (typically plant-pathogenic P. 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 among bacteriophages. 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". [13]
Since cells do not produce double-stranded RNA during normal nucleic acid metabolism, natural selection has favored the evolution of enzymes that destroy dsRNA on contact. The best known class of this type of enzymes is Dicer. It is hoped that broad-spectrum anti-virals could be synthesized that take advantage of this vulnerability of double-stranded RNA viruses. [14]
An RNA virus is a virus characterized by a ribonucleic acid (RNA) based genome. The genome can be single-stranded RNA (ssRNA) or double-stranded (dsRNA). Notable human diseases caused by RNA viruses include influenza, SARS, MERS, COVID-19, Dengue virus, hepatitis C, hepatitis E, West Nile fever, Ebola virus disease, rabies, polio, mumps, and measles.
Sedoreoviridae is a family of double-stranded RNA viruses. Member viruses have a wide host range, including vertebrates, invertebrates, plants, protists and fungi. They lack lipid envelopes and package their segmented genome within multi-layered capsids. Lack of a lipid envelope has allowed three-dimensional structures of these large complex viruses to be obtained, revealing a structural and likely evolutionary relationship to the cystovirus family of bacteriophage. There are currently 97 species in this family, divided among 15 genera in two subfamilies. Reoviruses can affect the gastrointestinal system and respiratory tract. The name "reo-" is an acronym for "respiratory enteric orphan" viruses. The term "orphan virus" refers to the fact that some of these viruses have been observed not associated with any known disease. Even though viruses in the family Reoviridae have more recently been identified with various diseases, the original name is still used.
Picornaviruses are a group of related nonenveloped RNA viruses which infect vertebrates including fish, mammals, and birds. They are viruses that represent a large family of small, positive-sense, single-stranded RNA viruses with a 30 nm icosahedral capsid. The viruses in this family can cause a range of diseases including the common cold, poliomyelitis, meningitis, hepatitis, and paralysis.
Cystovirus is a genus of double-stranded RNA viruses which infects bacteria. It is the only genus in the family Cystoviridae. The name of the group cysto derives from Greek kystis which means bladder or sack. There are seven species in this genus.
Birnaviridae is a family of double-stranded RNA viruses. Salmonid fish, birds and insects serve as natural hosts. There are currently 11 species in this family, divided among seven genera. Diseases associated with this family include infectious pancreatic necrosis in salmonid fish, which causes significant losses to the aquaculture industry, with chronic infection in adult salmonid fish and acute viral disease in young salmonid fish.
Infectious bursal disease (IBD), also known as Gumboro disease, infectious bursitis, and infectious avian nephrosis, is a highly contagious disease of young chickens and turkeys caused by infectious bursal disease virus (IBDV), characterized by immunosuppression and mortality generally at 3 to 6 weeks of age. The disease was first discovered in Gumboro, Delaware in 1962. It is economically important to the poultry industry worldwide due to increased susceptibility to other diseases and negative interference with effective vaccination. In recent years, very virulent strains of IBDV (vvIBDV), causing severe mortality in chicken, have emerged in Europe, Latin America, South-East Asia, Africa, and the Middle East. Infection is via the oro-fecal route, with affected birds excreting high levels of the virus for approximately 2 weeks after infection. The disease is easily spread from infected chickens to healthy chickens through food, water, and physical contact.
Φ6 is the best-studied bacteriophage of the virus family Cystoviridae. It infects Pseudomonas bacteria. 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 among bacteriophages. 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".
Orbivirus is a genus of double-stranded RNA viruses in the family Reoviridae and subfamily Sedoreovirinae. Unlike other reoviruses, orbiviruses are arboviruses. They can infect and replicate within a wide range of arthropod and vertebrate hosts. Orbiviruses are named after their characteristic doughnut-shaped capsomers.
Orthoreovirus is a genus of viruses, in the family Reoviridae, in the subfamily Spinareovirinae. Vertebrates serve as natural hosts. There are ten species in this genus. Diseases associated with this genus include mild upper respiratory tract disease, gastroenteritis, and biliary atresia. Mammalian orthoreovirus 3 induces cell death preferentially in transformed cells and therefore displays inherent oncolytic properties.
Aphthovirus is a viral genus of the family Picornaviridae. Aphthoviruses infect split-hooved animals, and include the causative agent of foot-and-mouth disease, Foot-and-mouth disease virus (FMDV). There are seven FMDV serotypes: A, O, C, SAT 1, SAT 2, SAT 3 and Asia 1, and four non-FMDV serotypes belonging to three additional species Bovine rhinitis A virus (BRAV), Bovine rhinitis B virus (BRBV) and Equine rhinitis A virus (ERAV).
Cypovirus, short for cytoplasmic polyhedrosis virus, is a genus of double-stranded RNA viruses in the family Reoviridae and subfamily Spinareovirinae, isolated solely from insects. Associated diseases include chronic diarrhoea and pale blue iridescence in the guts of larvae. It contains sixteen species.
Wound tumor virus is an invertebrate and plant virus found in the United States of America belonging to the genus Phytoreovirus and the family Reoviridae. It is a type III virus under the Baltimore classification system; that is it has a double-stranded RNA genome. This genome is approximately 25,000 base pairs long and organised into twelve segments. All the viral replication occurs in the cytoplasm. The virus is 22% RNA by weight, the other 78% being structural proteins.
Phytoreovirus is a genus of viruses, in the family Reoviridae, in the subfamily Sedoreovirinae. They are non-turreted reoviruses that are major agricultural pathogens, particularly in Asia. Oryza sativa for RDV and RGDV, dicotyledonous for WTV, and leafhoppers serve as natural hosts. There are three species in this genus. Diseases associated with this genus include: WTV: galls (tumor). RDV: dwarf disease of rice. RGDV: dwarfing, stunting, and galls.
Bidensovirus is a genus of single stranded DNA viruses that infect invertebrates. The species in this genus were originally classified in the family Parvoviridae but were moved to a new genus because of significant differences in the genomes.
Major capsid protein VP1 is a viral protein that is the main component of the polyomavirus capsid. VP1 monomers are generally around 350 amino acids long and are capable of self-assembly into an icosahedral structure consisting of 360 VP1 molecules organized into 72 pentamers. VP1 molecules possess a surface binding site that interacts with sialic acids attached to glycans, including some gangliosides, on the surfaces of cells to initiate the process of viral infection. The VP1 protein, along with capsid components VP2 and VP3, is expressed from the "late region" of the circular viral genome.
Xi River virus (XRV) is a putative novel bat virus in the genus Orthoreovirus isolated from fruit bats in Guangdong Province in southern China. It is the first bat reovirus isolated in China.
Kadipiro virus (KDV) is a member of the virus family Reoviridae. It is an arbovirus and has been isolated from Culex, Anopheles, Armigeres, and Aedes mosquitoes in Indonesia and China. Other members of the genus Seadornavirus have been linked to viral encephalitis.
Epizootic hemorrhagic disease virus, often abbreviated to EHDV, is a species of the genus Orbivirus, a member of the family Reoviridae. It is the causative agent of epizootic hemorrhagic disease, an acute, infectious, and often fatal disease of wild ruminants. In North America, the most severely affected ruminant is the white-tailed deer, although it may also infect mule deer, black-tailed deer, elk, bighorn sheep, and pronghorn antelope. It is often mistakenly referred to as “bluetongue virus” (BTV), another Orbivirus that like EHDV causes the host to develop a characteristic blue tongue due to systemic hemorrhaging and lack of oxygen in the blood. Despite showing clinical similarities, these two viruses are genetically distinct.
Triatoma virus (TrV) is a virus belonging to the insect virus family Dicistroviridae. Within this family, there are currently 3 genera and 15 species of virus. Triatoma virus belongs to the genus Cripavirus. It is non-enveloped and its genetic material is positive-sense, single-stranded RNA. The natural hosts of triatoma virus are invertebrates. TrV is a known pathogen to Triatoma infestans, the major vector of Chagas disease in Argentina which makes triatoma virus a major candidate for biological vector control as opposed to chemical insecticides. Triatoma virus was first discovered in 1984 when a survey of pathogens of triatomes was conducted in the hopes of finding potential biological control methods for T. infestans.
Mammalian orthoreovirus (MRV) is a double-stranded RNA virus. It is a part of the family Reoviridae, as well as the subfamily Spinareovirinae. As seen in the name, the Mammalian Ortheoreovirus infects numerous mammalian species and vertebrates which serve as natural hosts. Some diseases that occur as a result of this virus or are associated with this virus include mild upper respiratory illness, and gastrointestinal illness. Examples of these are: upper respiratory tract syndromes, gastroenteritis, biliary atresia, obstructive hydrocephalus, jaundice, alopecia, conjunctivitis, and ‘oily hair’ associated with steatorrhea.
...a new broad-spectrum antiviral approach, dubbed Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO)...