''Torovirus'' is a genus of
enveloped,
positive-strand RNA virus
Positive-strand RNA viruses (+ssRNA viruses) are a group of related viruses that have positive-sense, single-stranded genomes made of ribonucleic acid. The positive-sense genome can act as messenger RNA (mRNA) and can be directly translated int ...
es in the order ''
Nidovirales'' and family ''
Tobaniviridae''.
They primarily infect
vertebrate
Vertebrates () comprise all animal taxa within the subphylum Vertebrata () (chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with c ...
s, especially cattle, pigs, and horses.
Diseases associated with this genus include
gastroenteritis,
[ which commonly presents in mammals.] ''Torovirus'' is the only genus in the monotypic
In biology, a monotypic taxon is a taxonomic group (taxon) that contains only one immediately subordinate taxon. A monotypic species is one that does not include subspecies or smaller, infraspecific taxa. In the case of genera, the term "unispe ...
subfamily ''Torovirinae''. ''Torovirus'' is also a monotypic taxon, containing only one subgenus, ''Renitovirus''.
The discovery of the first torovirus can be traced back to 1970s. Equine torovirus (EToV) was accidentally found in the rectal sample from a horse who was experiencing severe diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...
. The 'Breda' bovine torovirus was later found in 1979 while investigation in a dairy farm in Breda. They had several calves experiencing severe diarrhea for months. In 1984, torovirus-like particles were detected with electron microscope
An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...
(EM) technique in the human patients with gastroenteritis.[Cho, K. O., & Hoet, A. E. (2014). Toroviruses (Coronaviridae). Reference Module in Biomedical Sciences, B978-0-12-801238-3.02674-X. https://doi.org/10.1016/B978-0-12-801238-3.02674-X]
Virology
Structure
Toroviruses (ToV) are single-stranded RNA viruses that have a peplomer-bearing envelope that is often correlated with the enteric infections in cattle and possibly humans. These viruses appear to occur globally, occurrence of ToVs have been reported from countries in various continents like Europe, Americas, New Zealand and South Africa. Torovirus particles typically possess a helical and symmetrical nucleocapsid that is coiled into a hollow cylindrical shape. The diameter is approximately 23 nm with an average length of 104 nm, where every turn cycle is at intervals of 4.5 nm.
ToVs are pleomorphic, with size ranging from 100 nm to 150 nm with club-like outgrowths extending from the capsid. A nucleocapsid that is doughnut-shaped with helical symmetry is also discovered in ''Toroviruses''.[ICTVdB Management (2006). 03.019.0.02. Torovirus. In: ICTVdB - The Universal Virus Database, version 4. Büchen-Osmond, C. (Ed), Columbia University, New York, USA] Among various species of the ''Toroviruses'', only equine torovirus (EToV) can be grown in the cell culture medium due to which EToVs have been most extensively studied. The information from immunofluorescence studies and morphology of the bovine Toroviruses (BToV) intestinal cells has shown similarities among the EToVs and BToVs.
''Torovirus'' share some common characteristics with members of the related family Coronaviridae as they are round, pleomorphic, enveloped virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsk ...
es about 120 to 140 nm in diameter.
Genome
Toroviruses have a single piece of single-stranded, positive-sense RNA. The total length is approximately 25-30kb and they possess a complex replication mechanisms that includes the use of subgenomic mRNA
Subgenomic mRNAs are essentially smaller sections of the original transcribed template strand.
3' to 5' DNA or RNA
During transcription, the original template strand is usually read from the 3' to the 5' end from beginning to end. Subgenomic ...
, ribosomal frameshifting
Ribosomal frameshifting, also known as translational frameshifting or translational recoding, is a biological phenomenon that occurs during translation that results in the production of multiple, unique proteins from a single mRNA. The process can ...
, and polymerase stuttering. The genomic length of bovine torovirus is approximately 28.5 kb that is mainly comprised by one gene, replicase gene (20.2 kb). This gene contains two open reading frames
In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible readin ...
, ORF1a and ORF1b that encodes proteins pp1a and pp1b. The first genomic sequence of the PToV (porcine torovirus) was done in Shanghai, China in 2014. Genome length of porcine Torovirus was found to be 28301 bp and possess 79% sequence identity with the bovine Torovirus genome.
Life cycle
Cattle, pig, and horse serve as the natural host of Toroviruses and infection is thought to be via the faecal-oral route.
The Torovirus genome encodes for various structural proteins like spikes (S), membrane proteins (M), haemagglutinin‐esterase (HE) and nucleocapsid (N) which provides them the structural characterization necessary for infection and completing their life cycle. The first three proteins coding regions are deleted in the BEV species which enables them to grow in the cell culture, while other species are unable to grow in cell culture. The initial two-thirds of the torovirus genome has two open reading frames
In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible readin ...
, ORF1a and ORF1b. ORFb1 encloses a domain that encodes for the enzymes such as RNA dependent RNA polymerase
RNA-dependent RNA polymerase (RdRp) or RNA replicase is an enzyme that catalyzes the replication of RNA from an RNA template. Specifically, it catalyzes synthesis of the RNA strand complementary to a given RNA template. This is in contrast to ...
(RdRp) and the helicase
Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separatin ...
(Hel) that are necessary for transcription and translation of the virus.
Life cycle of Toroviruses involves replication within the infected host cell. These viruses predominantly bud into the lumen of the Golgi cisternae in the cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
. EToV can be seen within various parts of the Golgi apparatus
The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ...
and in the extracellular regions as well. The nucleocapsids of these viruses in the extracellular region has characteristic torus shape, whereas these nucleocapsids are rod shaped prior to budding to the host cell, which points to some morphological change happening in the maturation stage of the virus. Moreover, the nucleocapsids of the BToV and EToV are also found to accumulate in the nucleus of the infected cell.
Clinical signs and diagnosis
In cattle, the disease causes diarrhoea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
and systemic signs such as pyrexia
Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
, lethargy
Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwo ...
and anorexia. In calves, it may cause neurological signs and lead to death in some cases.
Many diagnostic techniques for torovirus infection in clinical specimens are now available such as hemagglutination
Hemagglutination, or haemagglutination, is a specific form of agglutination that involves red blood cells (RBCs). It has two common uses in the laboratory: blood typing and the quantification of virus dilutions in a haemagglutination assay.
Blood ...
(HA), enzyme-linked immunosorbent assay (ELISA
The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
), immune electron microscopy, hemagglutination-inhibition tests (HA/HI), and nucleic acid hybridization. Mostly torovirus infecting humans are probably closely related to BRV or BEV and relate to any previous history of some enteric
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
disease or infection. It is also the reason that the molecular techniques are considered more promising than the serological assays.
Pigs can be infected without showing any signs and symptoms that are physically visible.
Diagnosis of the viral infection involves electron microscopy, ELISA
The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
or haemagglutination inhibition.
Treatment and control
Supportive treatment may be given to prevent dehydration
In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...
and secondary infections.
Control relies on good biosecurity
Biosecurity refers to measures aimed at preventing the introduction and/or spread of harmful organisms (e.g. viruses, bacteria, etc.) to animals and plants in order to minimize the risk of transmission of infectious disease. In agriculture, thes ...
measures including prompt isolation and disinfection
A disinfectant is a chemical substance or compound used to inactivate or destroy microorganisms on inert surfaces. Disinfection does not necessarily kill all microorganisms, especially resistant bacterial spores; it is less effective than st ...
of premises.
As torovirus infections usually interrelates with severe diarrhea, it often led to dehydration. The most common treatment includes giving liquid therapies to the younger patients as the infection is most common in younger human population as well as in cattle. There are no as such specific preventive measures for the Torovirus infection control. Good hygiene and biosecurity practices are effective in prevention of the torovirus infection. Moreover, Antibody-containing colostrum can be given to the patients with estimated dose of 500ml/day.
The natural course of infection mostly researched is done in the cattle as the virus origin is related to the enteric disease in the cattle. In an experiment associated with the infection of cattle gave the results that the virus commonly transmit itself under conventional conditions. The initial symptoms in the calves showed the development of diarrhea in first 2 to 3 days of the infection. Most of the calves had the mild dehydration
In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...
and a few developed a mild fever. However, none of the cases required any therapeutic intervention and were treated usually with the changes in the diet of the infected calves.
A research by (Vanopdenbosch et al., 1992a) published a study that torovirus respiratory infections emerges mainly in the first month of life and from 4 to 6 months of age in the autumn season peak. In all those infections, about 25% infections lead to sudden death. Besides other causes like diarrhea, pneumonia
Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severi ...
and respiratory problems, central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
related symptoms have also been reported in some incidental cases.
Studies also reveals that the young calves infected with the torovirus need to be given fluid therapies as their body cold face severe dehydration during the infection. However, the adults recover by their immune response without any external treatment if any additional infections are not present. Many researchers also suggest that the disinfection and heat sterilization could easily destroy the virus but no scientific data or reports of such results are available so far.
Human torovirus
In 1984, torovirus like particles were observed in human patients with gastroenteritis or severe diarrhea. A number of case studies then started to emerge from various parts of the world. Torovirus like particles (ToVL) was reported in scientific studies from USA, France, The Netherlands, Canada, Great Britain, India and Brazil.
The presence of the ToVL was reported mainly in children and adults with severe diarrhea. The term human torovirus (HuTV) is often used to describe the ToVL particles.
Because there is much similarity in HuTV and BoTV, there are certain criterion that is followed in the detecting and differentiation of both strains.
Numerous studies have been conducted in the past to relate the toroviruses and its pathogenicity. Toroviruses has been found in various intestinal diseases in the children as well as the adults. A study of fecal excretion of Torovirus concluded that out of 206 examined cases, in around 72 (35%) cases the torovirus was found. As compared to the infections by rotavirus or torovirus, Toroviruses were more frequently found in the people that are more immunocompromised. The torovirus infections were characterized by reduced vomiting and increased bloody diarrhea. The immune system's antibody response mainly developed in the grown-up children who were non-immunocompromised.
In addition to gastroenteritis, toroviruses has also been found in the infants with necrotizing enterocolitis
Necrotizing enterocolitis (NEC) is a devastating intestinal disease that affects premature or very low birth weight infants.Gephart S.M., Quinn M. A call to action to fight for equity and end necrotizing enterocolitis disparities. ''Adv. Neonata ...
. However, in the same study, the severity of illness and mortality was not much affected in the patients with torovirus as compared to the patients who tested negative for torovirus.
Antigenic properties and pathogenicity
Bovine toroviruses are proposed to have mainly two different serotypes: bovine torovirus serotype 1 (BoTV-1) and bovine torovirus serotype 2 (BoTV-2).
Both serotypes of BoTV possess a hemagglutinin
In molecular biology, hemagglutinins (or ''haemagglutinin'' in British English) (from the Greek , 'blood' + Latin , 'glue') are receptor-binding membrane fusion glycoproteins produced by viruses in the '' Paramyxoviridae'' family. Hemagglutinins a ...
that reacts with erythrocytes from mice and rats, but not with human erythrocytes
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
. The BoTV does not elute from rat erythrocytes after 90 min at 36 °C. Both the serotypes of the bovine Torovirus possess a hemagglutinin that reacts with red blood cells in the rodents usually.[Woode GN, Reed DE, Runnels PL, Herrig MA and Hill HT (1982). Studies with an unclassified virus isolated from diarrheic calves. Veterinary Microbiology 7: 221–240.] No evidence so far suggests that reaction with the human erythrocytes.
Although, many recent studies revealed the presence of the torovirus in humans associated with many other enteric infections, diarrhea and conditions like gastroenteritis.
The exact mechanism by which the virus induces diarrhea is currently unknown, but the studies reveal that it could be due to infection and death of cells in the small intestine and villi crypts as well as the surface crypt enterocytes in the large intestine. It is also said that the watery diarrhea could be due to lesions in the colon that lead to reduction of water absorption by the cells in the large intestine.
The pathogenicity of the torovirus presence has been widely studied and explored in the bovine species, especially calves in the initial stage of life around 4 to 6 months of age.
Once the BoTV has been inoculated by an animal orally or nasally, it infects the epithelial
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...
cells of the villi and then extends to the components of the digestive system like the large intestine in the crypts of jejunum
The jejunum is the second part of the small intestine in humans and most higher vertebrates, including mammals, reptiles, and birds. Its lining is specialised for the absorption by enterocytes of small nutrient molecules which have been previou ...
, ileum
The ileum () is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine m ...
and colon. It ultimately results in diarrhea with in 24–72 hours of infection.
The antigens of BToV has also been reported in the dome epithelial cells and Microfold cell
Microfold cells (or M cells) are found in the gut-associated lymphoid tissue (GALT) of the Peyer's patches in the small intestine, and in the mucosa-associated lymphoid tissue (MALT) of other parts of the gastrointestinal tract. These cells are kn ...
s, present in Gut-associated lymphoid tissue
Gut-associated lymphoid tissue (GALT) is a component of the mucosa-associated lymphoid tissue (MALT) which works in the immune system to protect the body from invasion in the gut.
Owing to its physiological function in food absorption, the mucosa ...
of the Peyer's patch
Peyer's patches (or aggregated lymphoid nodules) are organized lymphoid follicles, named after the 17th-century Swiss anatomist Johann Conrad Peyer.
* Reprinted as:
* Peyer referred to Peyer's patches as ''plexus'' or ''agmina glandularum'' (c ...
in small intestine.
Some researchers suggest that the BToV only infects absorptive enterocytes. However, there are researchers that also suggest that the viral replication could start in the immature epithelial cells of the crypts and can further spread to the villi.
History
The discovery of the first torovirus can be traced back to 1970s. Equine torovirus (EToV) was accidentally found in the rectal sample from a horse who had severe diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...
. The 'Breda' bovine torovirus was later found in 1979 while investigation in a dairy farm in Breda. They had several calves who had had severe diarrhea for months. In 1984, torovirus-like particles were detected with electron microscope
An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...
(EM) technique in the human patients with gastroenteritis.
In 1972, a virus was isolated from a horse in Berne, Switzerland. The virus did not react with antisera against known equine viruses and was shown to have a unique morphology and substructure. In 1982 a similar, unclassified virus was isolated from calves in Breda, Iowa. In 1984 particles resembling these viruses were discovered in the faeces of humans. A new family of viruses—Toroviridae—was proposed at the 6th International Congress on the Taxonomy of Viruses in 1984, at Sendai, Japan. However, the family is currently assigned as family Tobaniviridae with subfamily ''Torovirinae'', order Nidovirales.
Taxonomy
Until recently, the toroviruses were not assigned any family. The recent molecular analysis of the virus revealed its similarities with Arterivirus and coronaviruses, which led to the inclusion of the Torovirus along with the Arterivirus in the previously monogeneric Coronaviridae. At present, toroviruses are included in the order Nidovirales sub family Torovirinae, family Tobaniviridae. Resemblance, molecular and genetic similarities, virion
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's ...
dimensions, behavioral ties and other characteristic similarities and differences are observed by the researchers for the taxonomic classification of the virus. In the toroviruses, the Berne virus has been extensively studied at the molecular level as compared to its other members. In 1992, the International Committee on Taxonomy of Viruses
The International Committee on Taxonomy of Viruses (ICTV) authorizes and organizes the taxonomic classification of and the nomenclatures for viruses. The ICTV has developed a universal taxonomic scheme for viruses, and thus has the means to ap ...
ICTV got enough data to consider torovirus in the coronavirus family due to the similarities in structure, replication behavior and the genetic sequencing.
Evolution
Toroviruses, Coronaviruses and arteriviruses are in the order '' Nidovirales'', a group of non segmented, positive sense single stranded animal viruses. Despite the differences in their genome size, varying host range and their replication strategies, the similarities in the sequence identities of the replicase proteins among different species of order Nidovirales ensures their common ancestry. Sequence analysis and comparison of the polymerase and helicase
Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separatin ...
domains of coronaviruses and toroviruses reveled 40-45% identical amino acids in both families, providing evidences of large evolutionary distance between the two families.[Snijder, E. J., and M. C. Horzinek. 1993. Toroviruses: replication, evolution and comparison with other members of the coronavirus-like superfamily. J. Gen. Virol.74:2305-2316]
References
External links
Toroviruses
reviewed and published by Wikivet, accessed 08/10/2011
Virus Pathogen Database and Analysis Resource (ViPR): Coronaviridae
ICTV
{{Taxonbar, from=Q176610, from2=Q57754811, from3=Q16880647
Torovirinae
Virus genera