94-530: Coronaviruses are a group of related RNA viruses that cause diseases in mammals and birds . In humans and birds, they cause respiratory tract infections that can range from mild to lethal. Mild illnesses in humans include some cases of the common cold (which is also caused by other viruses, predominantly rhinoviruses ), while more lethal varieties can cause SARS , MERS and COVID-19 . In cows and pigs they cause diarrhea , while in mice they cause hepatitis and encephalomyelitis . Coronaviruses constitute
188-435: A cross-species jump . Later in the 1890s, human coronavirus OC43 diverged from bovine coronavirus after another cross-species spillover event. It is speculated that the flu pandemic of 1890 may have been caused by this spillover event, and not by the influenza virus , because of the related timing, neurological symptoms, and unknown causative agent of the pandemic. Besides causing respiratory infections, human coronavirus OC43
282-679: A mortality rate of approximately 34.5%. In December 2019, a pneumonia outbreak was reported in Wuhan , China. On 31 December 2019, the outbreak was traced to a novel strain of coronavirus, which was given the interim name 2019-nCoV by the World Health Organization, later renamed SARS-CoV-2 by the International Committee on Taxonomy of Viruses . As of 10 March 2023, there were at least 6,881,955 confirmed deaths and more than 676,609,955 confirmed cases in
376-403: A positive or negative sense strand , and dsRNA viruses have both. This structure of the genome is important in terms of transcription to synthesize viral mRNA as well as replication of the genome, both of which are carried out by the viral enzyme RNA-dependent RNA polymerase (RdRp), also called RNA replicase. Positive-strand RNA viruses have genomes that can function as mRNA, so transcription
470-493: A proofreading function which the RNA-dependent RNA polymerase lacks. Replication – One of the main functions of the complex is to replicate the viral genome. RdRp directly mediates the synthesis of negative-sense genomic RNA from the positive-sense genomic RNA. This is followed by the replication of positive-sense genomic RNA from the negative-sense genomic RNA. Transcription – The other important function of
564-597: A slippery sequence (UUUAAAC) and a downstream RNA pseudoknot at the end of open reading frame ORF1a. The ribosomal frameshift allows for the continuous translation of ORF1a followed by ORF1b. The polyproteins have their own proteases , PLpro (nsp3) and 3CLpro (nsp5), which cleave the polyproteins at different specific sites. The cleavage of polyprotein pp1ab yields 16 nonstructural proteins (nsp1 to nsp16). Product proteins include various replication proteins such as RNA-dependent RNA polymerase ( nsp12 ), RNA helicase (nsp13), and exoribonuclease (nsp14). A number of
658-410: A 5′ methylated cap and a 3′ polyadenylated tail, which allows it to act like a messenger RNA and be directly translated by the host cell's ribosomes . The host ribosomes translate the initial overlapping open reading frames ORF1a and ORF1b of the virus genome into two large overlapping polyproteins, pp1a and pp1ab. The larger polyprotein pp1ab is a result of a -1 ribosomal frameshift caused by
752-626: A common ancestor with a bat coronavirus (ARCoV.2) between 1190 and 1449 CE. The human coronavirus 229E shared a common ancestor with a bat coronavirus (GhanaGrp1 Bt CoV) between 1686 and 1800 CE. More recently, alpaca coronavirus and human coronavirus 229E diverged sometime before 1960. MERS-CoV emerged in humans from bats through the intermediate host of camels. MERS-CoV, although related to several bat coronavirus species, appears to have diverged from these several centuries ago. The most closely related bat coronavirus and SARS-CoV diverged in 1986. The ancestors of SARS-CoV first infected leaf-nose bats of
846-464: A complete -ssRNA genome can be synthesized. -ssRNA viruses vary between those that initiate transcription by the RdRp creating a cap on the 5'-end (usually pronounced "five prime end") of the genome or by snatching a cap from host mRNA and attaching it to the viral RNA. For many -ssRNA viruses, at the end of transcription, RdRp stutters on a uracil in the genome, synthesizing hundreds of adenines in
940-513: A coronavirus is 5′-leader-UTR -replicase (ORF1ab)-spike (S)-envelope (E)-membrane (M)-nucleocapsid (N)- 3′UTR -poly (A) tail. The open reading frames 1a and 1b, which occupy the first two-thirds of the genome, encode the replicase polyprotein (pp1ab). The replicase polyprotein self cleaves to form 16 nonstructural proteins (nsp1–nsp16). The later reading frames encode the four major structural proteins: spike , envelope , membrane , and nucleocapsid . Interspersed between these reading frames are
1034-674: A global alert soon after. The WHO update on 28 September 2012 said the virus did not seem to pass easily from person to person. However, on 12 May 2013, a case of human-to-human transmission in France was confirmed by the French Ministry of Social Affairs and Health. In addition, cases of human-to-human transmission were reported by the Ministry of Health in Tunisia . Two confirmed cases involved people who seemed to have caught
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#17327647637741128-405: A large number of animal coronaviruses identified since the 1960s. Coronaviruses are large, roughly spherical particles with unique surface projections. Their size is highly variable with average diameters of 80 to 120 nm . Extreme sizes are known from 50 to 200 nm in diameter. The total molecular mass is on average 40,000 kDa . They are enclosed in an envelope embedded with
1222-424: A matrix-like lattice that adds to the extra-thickness of the envelope. Different species can have either N - or O -linked glycans in their protein amino-terminal domain. The M protein is crucial during the assembly, budding , envelope formation, and pathogenesis stages of the virus lifecycle. The E proteins are minor structural proteins and highly variable in different species. There are only about 20 copies of
1316-438: A number of protein molecules. The lipid bilayer envelope, membrane proteins, and nucleocapsid protect the virus when it is outside the host cell. The viral envelope is made up of a lipid bilayer in which the membrane (M), envelope (E) and spike (S) structural proteins are anchored. The molar ratio of E:S:M in the lipid bilayer is approximately 1:20:300. The E and M protein are the structural proteins that combined with
1410-483: A reduced number of progeny, so viral genomes typically contain sequences that are highly conserved over time with relatively few mutations. Many RdRp-encoding RNA viruses also experience a high rate of genetic recombination , though rates of recombination vary significantly, with lower rates in -ssRNA viruses and higher rates in dsRNA and +ssRNA viruses. There are two types of recombination: copy choice recombination and reassortment. Copy choice recombination occurs when
1504-430: A row as part of creating a polyadenylated tail for the mRNA. Some -ssRNA viruses are essentially ambisense, and have proteins encoded by both the positive and negative strand, so mRNA is synthesized directly from the genome and from a complementary strand. For dsRNA viruses, RdRp transcribes mRNA by using the negative strand as a template. Positive strands may also be used as templates to synthesize negative strands for
1598-488: A schoolboy in Epsom, Surrey, was different as it could not be maintained in any of the culture media. The specimen designated B814 when experimented on healthy volunteers was highly contagious and produced the symptoms of cold within a few days. Due to its unusual nature, they were uncertain whether the pathogen was a virus or a bacterium. Without any other method to study, the specimen was preserved for four years. Returning from
1692-564: A seasonal incidence occurring in the winter months in temperate climates . There is no preponderance in any season in tropical climates . In 2003, following the outbreak of severe acute respiratory syndrome (SARS) which had begun the prior year in Asia, and secondary cases elsewhere in the world, the World Health Organization (WHO) issued a press release stating that a novel coronavirus identified by several laboratories
1786-462: A series of papers on his new technique in The Lancet in 1960. With researchers from University College London , he also investigated the role of human parvovirus B19 during 1985–1987. They discovered that the virus is the causative agent of erythematous rash illness and temporary stoppage of blood formation in persons with chronic haemolytic anaemia . Tyrrell was elected a Fellow of
1880-416: A short carboxy terminal end and has a net negative charge due to excess of acidic over basic amino acid residues. Coronaviruses contain a positive-sense, single-stranded RNA genome. The genome size for coronaviruses ranges from 26.4 to 31.7 kilobases . The genome size is one of the largest among RNA viruses. The genome has a 5′ methylated cap and a 3′ polyadenylated tail . The genome organization for
1974-537: A single jelly roll fold , so named because the folded structure of the protein contains a structure that resembles a jelly roll . Many also possess an envelope , a type of lipid membrane that typically surrounds the capsid. In particular, the viral envelope is near-universal among negative-sense, single-stranded (-ssRNA) viruses. Viruses in Orthornavirae have three different types of genomes: dsRNA, +ssRNA, and -ssRNA. Single-stranded RNA viruses have either
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#17327647637742068-547: A single virion, typically individual segments are swapped. Both forms of recombination can only occur if more than one virus is present in a cell, and the more alleles are present, the more likely recombination is to occur. A key difference between copy choice recombination and reassortment is that copy choice recombination can occur anywhere in a genome, whereas reassortment swaps fully-replicated segments. Therefore, copy choice recombination can produce non-functional viral proteins whereas reassortment cannot. The mutation rate of
2162-597: A time period of major advancements in molecular biology, including the discovery of mRNA as the immediate carrier of genetic information for protein synthesis. Tobacco mosaic virus was discovered in 1898 and was the first virus to be discovered. Viruses in the kingdom that are transmitted by arthropods have been a key target in the development of vector control , which often aims to prevent viral infections. In modern history, numerous disease outbreaks have been caused by RdRp-encoding RNA viruses, including outbreaks caused by coronaviruses, ebola, and influenza. Orthornavirae
2256-480: A unique pathogenesis because it causes both upper and lower respiratory tract infections . Six species of human coronaviruses are known, with one species subdivided into two different strains, making seven strains of human coronaviruses altogether. Four human coronaviruses produce symptoms that are generally mild, even though it is contended they might have been more aggressive in the past: Three human coronaviruses produce potentially severe symptoms: These cause
2350-540: A virus is associated with the rate of genetic recombinations. Higher mutation rates increase both the number of advantageous and disadvantageous mutations, whereas higher rates of recombination allows for beneficial mutations to be separated from deleterious ones. Therefore, higher rates of mutations and recombinations, up to a certain point, improve viruses' ability to adapt. Notable examples of this include reassortments that enable cross-species transmission of influenza viruses, which have led to numerous pandemics, as well as
2444-539: A virus, but was unique from all known cold viruses based on its antigenic property and symptoms it produced. Tyrrell and Malcolm L. Bynoe reported the discovery in the 5 June 1965 issue of the British Medical Journal , concluding: "After considerable initial doubts we now believe that the B814 strain is a virus virtually unrelated to any other known virus of the human respiratory tract, although, since it
2538-542: A visit to the Lund University in Sweden in 1965, Andrewes told Tyrrell that there was a young Swedish surgeon who was able to grow complex viruses. The Swede was Bertil Hoorn who had developed a culture method using human trachea tissue. Tyrrell immediately invited Hoorn to visit CCU, and after which they were able to grow different viruses which could not be cultured earlier. Specimen B814 could then be confirmed as
2632-500: A younger brother Andrew. He attended elementary schools at Ashford, Middlesex. His family moved to Sheffield in 1940, where he completed secondary education at King Edward VII School . While studying medicine at the University of Sheffield he suffered from a detached retina, which meant he was exempted from military conscription, and had a lifelong preference for monocular microscopes. He graduated in 1948 and earned membership of
2726-475: Is a kingdom of viruses that have genomes made of ribonucleic acid (RNA), including genes which encode an RNA-dependent RNA polymerase (RdRp). The RdRp is used to transcribe the viral RNA genome into messenger RNA (mRNA) and to replicate the genome. Viruses in this kingdom share a number of characteristics which promote rapid evolution , including high rates of genetic mutation , recombination , and reassortment . Viruses in Orthornavirae belong to
2820-433: Is also capable of genetic recombination when at least two viral genomes are present in the same infected cell. RNA recombination appears to be a major driving force in determining genetic variability within a coronavirus species, the capability of a coronavirus species to jump from one host to another and, infrequently, in determining the emergence of novel coronaviruses. The exact mechanism of recombination in coronaviruses
2914-590: Is also suspected of playing a role in neurological diseases . In the 1950s, the human coronavirus OC43 began to diverge into its present genotypes . Phylogenetically, mouse hepatitis virus ( Murine coronavirus ), which infects the mouse's liver and central nervous system , is related to human coronavirus OC43 and bovine coronavirus. Human coronavirus HKU1, like the aforementioned viruses, also has its origins in rodents. Coronaviruses vary significantly in risk factor. Some can kill more than 30% of those infected, such as MERS-CoV , and some are relatively harmless, such as
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3008-405: Is estimated to have existed as recently as 8000 BCE , although some models place the common ancestor as far back as 55 million years or more, implying long term coevolution with bat and avian species. The most recent common ancestor of the alphacoronavirus line has been placed at about 2400 BCE, of the betacoronavirus line at 3300 BCE, of the gammacoronavirus line at 2800 BCE, and
3102-531: Is ether-labile, it may be a myxovirus ." This was the discovery of human coronavirus. But the virus was difficult to maintain in culture and the structure was difficult to study. In 1966, June Dalziel Almeida had just joined as an electron microscopist at the St Thomas's Hospital Medical School in London. She had earlier developed techniques for studying viruses under electron microscope, and had also studied
3196-476: Is in turn composed of an S1 and S2 subunit . The homotrimeric S protein is a class I fusion protein which mediates the receptor binding and membrane fusion between the virus and host cell. The S1 subunit forms the head of the spike and has the receptor-binding domain (RBD). The S2 subunit forms the stem which anchors the spike in the viral envelope and on protease activation enables fusion. The two subunits remain noncovalently linked as they are exposed on
3290-516: Is not necessary. However, +ssRNA will produce dsRNA forms as part of the process of replicating their genomes. From the dsRNA, additional positive strands are synthesized, which may be used as mRNA or for genomes for progeny. Because +ssRNA viruses create intermediate dsRNA forms, they have to avoid the host's immune system in order to replicate. +ssRNA viruses accomplish this by replicating in membrane-associated vesicles that are used as replication factories. For many +ssRNA viruses, subgenomic portions of
3384-409: Is the most important virus among stone fruit crops. Brome mosaic virus , while not causing significant economic losses, is found throughout much of the world and primarily infects grasses, including cereals. Diseases caused by RNA viruses in Orthornavirae have been known throughout much of history, but their cause was only discovered in modern times. As a whole, RNA viruses were discovered during
3478-419: Is unclear, but likely involves template switching during genome replication. The replicated positive-sense genomic RNA becomes the genome of the progeny viruses . The mRNAs are gene transcripts of the last third of the virus genome after the initial overlapping reading frame. These mRNAs are translated by the host's ribosomes into the structural proteins and many accessory proteins. RNA translation occurs inside
3572-595: Is used to refer to any member of the subfamily Orthocoronavirinae . As of 2020, 45 species are officially recognised. The earliest reports of a coronavirus infection in animals occurred in the late 1920s, when an acute respiratory infection of domesticated chickens emerged in North America. Arthur Schalk and M.C. Hawn in 1931 made the first detailed report which described a new respiratory infection of chickens in North Dakota . The infection of new-born chicks
3666-786: The Flavivirus and Phlebovirus genera are numerous and often transmitted to humans. Coronaviruses and influenza viruses cause disease in various vertebrates, including bats, birds, and pigs. Plant viruses in the kingdom are numerous and infect many economically important crops. Tomato spotted wilt virus is estimated to cause more than US$ 1 billion in damages annually, affecting more than 800 plant species including chrysanthemum, lettuce, peanut, pepper, and tomato. Cucumber mosaic virus infects more than 1,200 plant species and likewise causes significant crop losses. Potato virus Y causes significant reductions in yield and quality for pepper, potato, tobacco, and tomato, and Plum pox virus
3760-1024: The Baltimore classification system, which groups viruses together based on their manner of mRNA synthesis, and which is often used alongside standard virus taxonomy, which is based on evolutionary history. Those three groups are Group III: dsRNA viruses, Group IV: +ssRNA viruses, and Group V: -ssRNA viruses. RNA viruses are associated with a wide range of disease, including many of the most widely known viral diseases. Notable disease-causing viruses in Orthornavirae include: Animal viruses in Orthornavirae include orbiviruses , which cause various diseases in ruminants and horses, including Bluetongue virus , African horse sickness virus , Equine encephalosis virus , and epizootic hemorrhagic disease virus . The vesicular stomatitis virus causes disease in cattle, horses, and pigs. Bats harbor many viruses including ebolaviruses and henipaviruses , which also can cause disease in humans. Similarly, arthropod viruses in
3854-579: The COVID-19 pandemic . The Wuhan strain has been identified as a new strain of Betacoronavirus from group 2B with approximately 70% genetic similarity to the SARS-CoV. The virus has a 96% similarity to a bat coronavirus, so it is widely suspected to originate from bats as well. RNA viruses Positive-strand RNA viruses Negative-strand RNA viruses Double-stranded RNA viruses Ambisense RNA viruses Orthornavirae
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3948-475: The National Institute of Health the same year was able to isolate another member of this new group of viruses using organ culture and named one of the samples OC43 (OC for organ culture). Like B814, 229E, and IBV, the novel cold virus OC43 had distinctive club-like spikes when observed with the electron microscope. The IBV-like novel cold viruses were soon shown to be also morphologically related to
4042-502: The RNA world , suggesting that retroelements (retrotransposons and group II introns) originated from an ancestor related to the phylum Lenarviricota and that members of a newly discovered Taraviricota lineage (phylum) would be the ancestors of all RNA viruses. According to this study the genomes of both dsRNA, +ssRNA and -ssRNA evolved independently and were altered several times in evolution. RNA viruses that encode RdRp are assigned to
4136-912: The Royal College of Physicians in 1949. During those years he worked as a house physician at the Professorial Medical Unit of Sheffield Royal Hospital and at the City General Hospital in Sheffield. He was appointed as the first Research Registrar post under the Hospital Endowment Fund of Sheffield in 1950. He moved to the Rockefeller Institute in New York to work under Frank Horsfall as an assistant from 1951 to 1954. He
4230-460: The endoplasmic reticulum . The viral structural proteins S, E, and M move along the secretory pathway into the Golgi intermediate compartment . There, the M proteins direct most protein-protein interactions required for the assembly of viruses following its binding to the nucleocapsid . Progeny viruses are then released from the host cell by exocytosis through secretory vesicles. Once released
4324-401: The stellar corona , from which their name derives. The name "coronavirus" is derived from Latin corona , meaning "crown" or "wreath", itself a borrowing from Greek κορώνη korṓnē , "garland, wreath". The name was coined by June Almeida and David Tyrrell who first observed and studied human coronaviruses. The word was first used in print in 1968 by an informal group of virologists in
4418-508: The subfamily Orthocoronavirinae , in the family Coronaviridae , order Nidovirales and realm Riboviria . They are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The genome size of coronaviruses ranges from approximately 26 to 32 kilobases , one of the largest among RNA viruses. They have characteristic club-shaped spikes that project from their surface, which in electron micrographs create an image reminiscent of
4512-415: The virus to enter the host cell by endocytosis or direct fusion of the viral envelope with the host membrane . Coronaviruses can enter cells by either fusing to their lipid envelope with the cell membrane on the cell surface or by internalization via endocytosis. On entry into the host cell , the virus particle is uncoated , and its genome enters the cell cytoplasm . The coronavirus RNA genome has
4606-540: The April 1967 issue of the Journal of General Virology , writing: "Probably the most interesting finding from these experiments was that two human respiratory viruses, 229 E and B814 are morphologically identical with avian infectious bronchitis." The new discovery was supported by independent discovery of new human viruses ( OC43 ) by Kenneth McIntosh and co-workers at the National Institute of Health , Bethesda, almost at
4700-713: The Common Cold . He died of prostate cancer on 2 May 2005 at Salisbury. Tyrrell married Moyra Wylie, a general practitioner, in 1950. They had one son and two daughters. He was a devoted Christian and served as an organist and choirmaster at his local church. Soon after he joined CCU, Tyrrell developed a system of categorising cold viruses. Some viruses could be maintained only in human-embryo-kidney cell culture and were designated H strain, and others could be maintained both in human-embryo-kidney cell culture and monkey-embryo-kidney cell culture and were labelled M strain. One nasal swab sample collected on 17 February 1961 from
4794-415: The E protein molecule in a coronavirus particle. They are 8.4 to 12 kDa in size and are composed of 76 to 109 amino acids. They are integral proteins (i.e. embedded in the lipid layer) and have two domains namely a transmembrane domain and an extramembrane C-terminal domain. They are almost fully α-helical, with a single α-helical transmembrane domain, and form pentameric (five-molecular) ion channels in
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#17327647637744888-527: The RdRp switches templates during synthesis without releasing the prior, newly created RNA strand, which generates a genome of mixed ancestry. Reassortment , which is restricted to viruses with segmented genomes, has segments from different genomes packaged into a single virion, or virus particle, which also produces hybrid progeny. For reassortment, some segmented viruses package their genomes into multiple virions, which produces genomes that are random mixtures of parents, whereas for those that are packaged into
4982-432: The common cold. Coronaviruses can cause colds with major symptoms, such as fever, and a sore throat from swollen adenoids . Coronaviruses can cause pneumonia (either direct viral pneumonia or secondary bacterial pneumonia ) and bronchitis (either direct viral bronchitis or secondary bacterial bronchitis). The human coronavirus discovered in 2003, SARS-CoV , which causes severe acute respiratory syndrome (SARS), has
5076-466: The complex is to transcribe the viral genome. RdRp directly mediates the synthesis of negative-sense subgenomic RNA molecules from the positive-sense genomic RNA. This process is followed by the transcription of these negative-sense subgenomic RNA molecules to their corresponding positive-sense mRNAs . The subgenomic mRNAs form a " nested set " which have a common 5'-head and partially duplicate 3'-end. Recombination – The replicase-transcriptase complex
5170-776: The construction of genomic dsRNA. dsRNA is not a molecule produced by cells, so cellular life has evolved mechanisms to detect and inactivate viral dsRNA. To counter this, dsRNA viruses typically retain their genomes inside of viral capsid in order to evade the host's immune system. RNA viruses in Orthornavirae experience a high rate of genetic mutations because RdRp is prone to making errors in replication since it typically lacks proofreading mechanisms to repair errors. Mutations in RNA viruses are often influenced by host factors such as dsRNA-dependent adenosine deaminases , which edit viral genomes by changing adenosines to inosines . Mutations in genes that are essential for replication lead to
5264-482: The coronavirus species, by either an aerosol , fomite , or fecal-oral route . Human coronaviruses infect the epithelial cells of the respiratory tract , while animal coronaviruses generally infect the epithelial cells of the digestive tract . SARS coronavirus , for example, infects the human epithelial cells of the lungs via an aerosol route by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. Transmissible gastroenteritis coronavirus (TGEV) infects
5358-554: The deltacoronavirus line at about 3000 BCE. Bats and birds, as warm-blooded flying vertebrates, are an ideal natural reservoir for the coronavirus gene pool (with bats the reservoir for alphacoronaviruses and betacoronavirus – and birds the reservoir for gammacoronaviruses and deltacoronaviruses). The large number and global range of bat and avian species that host viruses have enabled extensive evolution and dissemination of coronaviruses. Many human coronaviruses have their origin in bats. The human coronavirus NL63 shared
5452-622: The disease from their late father, who became ill after a visit to Qatar and Saudi Arabia. Despite this, it appears the virus had trouble spreading from human to human, as most individuals who are infected do not transmit the virus. By 30 October 2013, there were 124 cases and 52 deaths in Saudi Arabia. After the Dutch Erasmus Medical Centre sequenced the virus, the virus was given a new name, Human Coronavirus–Erasmus Medical Centre (HCoV-EMC). The final name for
5546-432: The diseases commonly called SARS , MERS , and COVID-19 respectively. Although the common cold is usually caused by rhinoviruses , in about 15% of cases the cause is a coronavirus. The human coronaviruses HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63 continually circulate in the human population in adults and children worldwide and produce the generally mild symptoms of the common cold. The four mild coronaviruses have
5640-431: The electron beam used to scan the virus particle). The M protein is the main structural protein of the envelope that provides the overall shape and is a type III membrane protein . It consists of 218 to 263 amino acid residues and forms a layer 7.8 nm thick. It has three domains, a short N-terminal ectodomain , a triple-spanning transmembrane domain , and a C-terminal endodomain . The C-terminal domain forms
5734-526: The emergence of drug-resistance influenza strains via mutations that were reassorted. The exact origin of Orthornavirae is not well established, but the viral RdRp shows a relation to the reverse transcriptase (RT) enzymes of group II introns that encode RTs and retrotransposons , the latter of which are self-replicating DNA sequences that integrate themselves into other parts of the same DNA molecule. A larger study (2022) where new lieneages (phyla) were described, has suggested that RNA viruses descend from
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#17327647637745828-470: The envelope, there is the nucleocapsid , which is formed from multiple copies of the nucleocapsid (N) protein, which are bound to the positive-sense single-stranded RNA genome in a continuous beads -on-a-string type conformation. N protein is a phosphoprotein of 43 to 50 kDa in size, and is divided into three conserved domains. The majority of the protein is made up of domains 1 and 2, which are typically rich in arginines and lysines . Domain 3 has
5922-530: The first images of the rubella virus using immune-electronmicroscopy, Tyrrell and Almeida worked on characterising a new type of viruses, now called coronaviruses . He retired from the Common Cold Unit in 1990 and subsequently carried out research at the Centre for Applied Microbiology and Research at Porton Down , where he also worked on his scientific autobiography, Cold Wars: The Fight Against
6016-470: The first two coronaviruses discovered, infectious bronchitis virus (IBV) and mouse hepatitis virus (MHV). Tyrrell sent her the specimen, including one new human virus called 229E , which was recently discovered by Dorothy Hamre and John J. Procknow at the University of Chicago. Almeida revealed that the two human viruses were identical to each other, and to IBV as well. Almeida and Tyrrell reported in
6110-418: The genome will be transcribed to translate specific proteins, whereas others will transcribe a polyprotein that is cleaved to produce separate proteins. Negative-strand RNA viruses have genomes that function as templates from which mRNA can be synthesized directly by RdRp. Replication is the same process but executed on the positive sense antigenome, during which RdRp ignores all transcription signals so that
6204-416: The genus Hipposideridae ; subsequently, they spread to horseshoe bats in the species Rhinolophidae , then to Asian palm civets , and finally to humans. Unlike other betacoronaviruses, bovine coronavirus of the species Betacoronavirus 1 and subgenus Embecovirus is thought to have originated in rodents and not in bats. In the 1790s, equine coronavirus diverged from the bovine coronavirus after
6298-403: The journal Nature to designate the new family of viruses. The name refers to the characteristic appearance of virions (the infective form of the virus) by electron microscopy , which have a fringe of large, bulbous surface projections creating an image reminiscent of the solar corona or halo. This morphology is created by the viral spike peplomers , which are proteins on the surface of
6392-415: The kingdom Orthornavirae , which contains six official phyla, six unofficial phyla and several taxa that are unassigned to a phylum due to lack of information. The five phyla are separated based on the genome types, host ranges, and genetic similarity of member viruses. The unassigned taxa are listed hereafter (- viridae denotes family and - virus denotes genus). The kingdom contains three groups in
6486-407: The kingdom. The first part of Orthornavirae comes from Greek ὀρθός [orthós], meaning straight, the middle part, rna , refers to RNA, and - virae is the suffix used for virus kingdoms. RNA viruses in Orthornavirae typically do not encode many proteins, but most positive-sense, single-stranded (+ssRNA) viruses and some double-stranded RNA (dsRNA) viruses encode a major capsid protein that has
6580-437: The lipid bilayer to shape the viral envelope and maintain its size. S proteins are needed for interaction with the host cells. But human coronavirus NL63 is peculiar in that its M protein has the binding site for the host cell, and not its S protein. The diameter of the envelope is 85 nm. The envelope of the virus in electron micrographs appears as a distinct pair of electron-dense shells (shells that are relatively opaque to
6674-405: The lipid bilayer. They are responsible for virion assembly, intracellular trafficking and morphogenesis (budding). The spikes are the most distinguishing feature of coronaviruses and are responsible for the corona- or halo-like surface. On average a coronavirus particle has 74 surface spikes. Each spike is about 20 nm long and is composed of a trimer of the S protein. The S protein
6768-413: The members of betacoronavirus subgroup A ) also has a shorter spike-like surface protein called hemagglutinin esterase (HE). The HE proteins occur as homodimers composed of about 400 amino acid residues and are 40 to 50 kDa in size. They appear as tiny surface projections of 5 to 7 nm long embedded in between the spikes. They help in the attachment to and detachment from the host cell. Inside
6862-707: The most variable components as they are responsible for host cell specificity. They possess two major domains named N-terminal domain (S1-NTD) and C-terminal domain (S1-CTD), both of which serve as the receptor-binding domains. The NTDs recognize and bind sugars on the surface of the host cell. An exception is the MHV NTD that binds to a protein receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). S1-CTDs are responsible for recognizing different protein receptors such as angiotensin-converting enzyme 2 (ACE2), aminopeptidase N (APN), and dipeptidyl peptidase 4 (DPP4). A subset of coronaviruses (specifically
6956-613: The most widely known viral diseases are caused by members of this kingdom, including coronaviruses , the Ebola virus , influenza viruses , the measles virus , and the rabies virus , as well as the first virus ever discovered, tobacco mosaic virus . In modern history, RdRp-encoding RNA viruses have caused numerous disease outbreaks, and they infect many economically important crops. Most eukaryotic viruses, including most human, animal, and plant viruses, are RdRp-encoding RNA viruses. In contrast, there are relatively few prokaryotic viruses in
7050-515: The mouse hepatitis virus. This new group of viruses were named coronaviruses after their distinctive morphological appearance. Human coronavirus 229E and human coronavirus OC43 continued to be studied in subsequent decades. The coronavirus strain B814 was lost. It is not known which present human coronavirus it was. Other human coronaviruses have since been identified, including SARS-CoV in 2003, HCoV NL63 in 2003, HCoV HKU1 in 2004, MERS-CoV in 2013, and SARS-CoV-2 in 2019. There have also been
7144-657: The name coronavirus was born. At the Rockefeller Institute, Tyrrell worked on the epidemiology on poliomyelitis . He presented his findings at the second International Congress on Poliomyelitis in Copenhagen on 3–7 September 1951, and published in The Lancet at the end of the year. At CCU, he developed techniques for culturing different cold viruses. He was the first to grow certain cold viruses ( rhinoviruses ) using nasal epithelial cells. He published
7238-558: The nonstructural proteins coalesce to form a multi-protein replicase-transcriptase complex (RTC). The main replicase-transcriptase protein is the RNA-dependent RNA polymerase (RdRp). It is directly involved in the replication and transcription of RNA from an RNA strand. The other nonstructural proteins in the complex assist in the replication and transcription process. The exoribonuclease nonstructural protein, for instance, provides extra fidelity to replication by providing
7332-459: The novel virus by serially passing it through organ culture of human embryonic trachea . The new cultivating method was introduced to the lab by Bertil Hoorn. The isolated virus when intranasally inoculated into volunteers caused a cold and was inactivated by ether which indicated it had a lipid envelope . Dorothy Hamre and John Procknow at the University of Chicago isolated a novel cold from medical students in 1962. They isolated and grew
7426-615: The pig epithelial cells of the digestive tract via a fecal–oral route by binding to the alanine aminopeptidase (APN) receptor. Coronaviruses form the subfamily Orthocoronavirinae, which is one of two subfamilies in the family Coronaviridae , order Nidovirales , and realm Riboviria . They are divided into the four genera: Alphacoronavirus , Betacoronavirus , Gammacoronavirus and Deltacoronavirus . Alphacoronaviruses and betacoronaviruses infect mammals, while gammacoronaviruses and deltacoronaviruses primarily infect birds. The most recent common ancestor (MRCA) of all coronaviruses
7520-432: The reading frames for the accessory proteins. The number of accessory proteins and their function is unique depending on the specific coronavirus. Infection begins when the viral spike protein attaches to its complementary host cell receptor. After attachment, a protease of the host cell cleaves and activates the receptor-attached spike protein. Depending on the host cell protease available, cleavage and activation allows
7614-471: The realm Riboviria . They are descended from a common ancestor that may have been a non-viral molecule that encoded a reverse transcriptase instead of an RdRp for replication. The kingdom is subdivided into five phyla that separate member viruses based on their genome type, host range, and genetic similarity. Viruses with three genome types are included: positive-strand RNA viruses , negative-strand RNA viruses , and double-stranded RNA viruses . Many of
7708-555: The same time. It was becoming evident that all these viruses including MHV were of the same kind. Almeida and Tyrrell came up with the name "coronavirus". As Tyrrell recollected in Cold Wars: The Fight Against the Common Cold : We looked more closely at the appearance of the new viruses and noticed that they had a kind of halo surrounding them. Recourse to a dictionary produced the Latin equivalent, corona, and so
7802-449: The viral surface until they attach to the host cell membrane. In a functionally active state, three S1 are attached to two S2 subunits. The subunit complex is split into individual subunits when the virus binds and fuses with the host cell under the action of proteases such as cathepsin family and transmembrane protease serine 2 (TMPRSS2) of the host cell. S1 proteins are the most critical components in terms of infection. They are also
7896-466: The virus in kidney tissue culture , designating it 229E. The novel virus caused a cold in volunteers and, like B814, was inactivated by ether. Scottish virologist June Almeida at St Thomas' Hospital in London, collaborating with Tyrrell, compared the structures of IBV, B814 and 229E in 1967. Using electron microscopy the three viruses were shown to be morphologically related by their general shape and distinctive club-like spikes . A research group at
7990-733: The virus is Middle East respiratory syndrome coronavirus (MERS-CoV). The only U.S. cases (both survived) were recorded in May 2014. In May 2015, an outbreak of MERS-CoV occurred in the Republic of Korea , when a man who had traveled to the Middle East, visited four hospitals in the Seoul area to treat his illness. This caused one of the largest outbreaks of MERS-CoV outside the Middle East. As of December 2019, 2,468 cases of MERS-CoV infection had been confirmed by laboratory tests, 851 of which were fatal,
8084-561: The virus. The scientific name Coronavirus was accepted as a genus name by the International Committee for the Nomenclature of Viruses (later renamed International Committee on Taxonomy of Viruses ) in 1971. As the number of new species increased, the genus was split into four genera, namely Alphacoronavirus , Betacoronavirus , Deltacoronavirus , and Gammacoronavirus in 2009. The common name coronavirus
8178-418: The viruses can infect other host cells. Infected carriers are able to shed viruses into the environment. The interaction of the coronavirus spike protein with its complementary cell receptor is central in determining the tissue tropism , infectivity , and species range of the released virus. Coronaviruses mainly target epithelial cells . They are transmitted from one host to another host, depending on
8272-491: Was a British virologist who was the director of the Common Cold Unit , which investigated viruses that caused common colds. He discovered the first human coronavirus (designated B814) in 1965. With June Almeida he made the first comparative study of human and chicken coronaviruses in 1967, and invented the name coronavirus in 1968. Tyrrell was born on 19 June 1925 to Sidney Tyrrell and Agnes Kate Blewett. He had
8366-540: Was also appointed as head of the Division of Communicable Diseases in 1967 and then deputy director of the MRC's Clinical Research Centre at Northwick Park Hospital , Harrow, Middlesex, in 1970, while still attached to CCU. The Clinical Research Centre was closed in 1984 following which Tyrrell returned full time at CCU in 1985, and remained there until its official closure in 1990. In the 1960s, after June Almeida produced
8460-734: Was briefly enrolled in the US Army during the Korean War (1950–1953). In 1954, he gained an appointment as External Scientific Staff of the Medical Research Council at the Virus Research Laboratory in Sheffield, where he worked until 1957. Upon an invitation from Sir Harold Himsworth, Secretary of MRC, he moved to the MRC's Common Cold Unit on the outskirts of Salisbury on 1 April 1957, becoming its head from 1962 succeeding Christopher Andrewes . He
8554-638: Was characterized by gasping and listlessness with high mortality rates of 40–90%. Leland David Bushnell and Carl Alfred Brandly isolated the virus that caused the infection in 1933. The virus was then known as infectious bronchitis virus (IBV). Charles D. Hudson and Fred Robert Beaudette cultivated the virus for the first time in 1937. The specimen came to be known as the Beaudette strain. In the late 1940s, two more animal coronaviruses, JHM that causes brain disease (murine encephalitis) and mouse hepatitis virus (MHV) that causes hepatitis in mice were discovered. It
8648-566: Was established in 2019 as a kingdom within the realm Riboviria , intended to accommodate all RdRp-encoding RNA viruses. Prior to 2019, Riboviria was established in 2018 and included only RdRp-encoding RNA viruses. In 2019, Riboviria was expanded to also include reverse transcribing viruses, placed under the kingdom Pararnavirae , so Orthornavirae was established to separate RdRp-encoding RNA viruses from reversing transcribing viruses. David Tyrrell (physician) David Arthur John Tyrrell CBE FRS (19 June 1925 – 2 May 2005)
8742-817: Was not realized at the time that these three different viruses were related. Human coronaviruses were discovered in the 1960s using two different methods in the United Kingdom and the United States. E.C. Kendall, Malcolm Bynoe, and David Tyrrell working at the Common Cold Unit of the British Medical Research Council collected a unique common cold virus designated B814 in 1961. The virus could not be cultivated using standard techniques which had successfully cultivated rhinoviruses , adenoviruses and other known common cold viruses. In 1965, Tyrrell and Bynoe successfully cultivated
8836-466: Was the causative agent for SARS. The virus was officially named the SARS coronavirus (SARS-CoV). More than 8,000 people from 29 countries and territories were infected, and at least 774 died. In September 2012, a new type of coronavirus was identified, initially called Novel Coronavirus 2012, and now officially named Middle East respiratory syndrome coronavirus (MERS-CoV). The World Health Organization issued
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