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|Group:||Group IV ((+)ssRNA)|
Human coronavirus HKU1
|Group:||Group IV ((+)ssRNA)|
Human coronavirus HKU1
Coronaviruses are species in the genera of virus belonging to one of two subfamilies Coronavirinae and Torovirinae in the family Coronaviridae. Coronaviruses are enveloped viruses with a positive-sense RNA genome and with a nucleocapsid of helical symmetry. The genomic size of coronaviruses ranges from approximately 26 to 32 kilobases, extraordinarily large for an RNA virus. The name "coronavirus" is derived from the Latin corona, meaning crown or halo, and refers to the characteristic appearance of virions under electron microscopy (E.M.) with a fringe of large, bulbous surface projections creating an image reminiscent of the solar corona. This morphology is created by the viral spike (S) peplomers, which are proteins that populate the surface of the virus and determine host tropism. Coronaviruses are grouped in the order Nidovirales, named for the Latin nidus, meaning nest, as all viruses in this order produce a 3' co-terminal nested set of subgenomic mRNA's during infection.
Proteins that contribute to the overall structure of all coronaviruses are the spike (S), envelope (E), membrane (M) and nucleocapsid (N). In the specific case of the SARS coronavirus (see below), a defined receptor-binding domain on S mediates the attachment of the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2). Some coronaviruses (specifically the members of Betacoronavirus subgroup A) also have a shorter spike-like protein called hemagglutinin esterase (HE).
Coronaviruses were first described in the 1960s from the nasal cavities of patients with the common cold. These viruses were subsequently named human coronavirus 229E and human coronavirus OC43.
Coronaviruses primarily infect the upper respiratory and gastrointestinal tract of mammals and birds. Four to five different currently known strains of coronaviruses infect humans. The most publicized human coronavirus, SARS-CoV which causes SARS, has a unique pathogenesis because it causes both upper and lower respiratory tract infections and can also cause gastroenteritis. Coronaviruses are believed to cause a significant percentage of all common colds in human adults. Coronaviruses cause colds in humans primarily in the winter and early spring seasons. The significance and economic impact of coronaviruses as causative agents of the common cold are hard to assess because, unlike rhinoviruses (another common cold virus), human coronaviruses are difficult to grow in the laboratory. Coronaviruses can even cause pneumonia, either direct viral pneumonia or a secondary bacterial pneumonia.
In chickens, the infectious bronchitis virus (IBV), a coronavirus, targets not only the respiratory tract but also the uro-genital tract. The virus can spread to different organs throughout the chicken.
Coronaviruses also cause a range of diseases in farm animals and domesticated pets, some of which can be serious and are a threat to the farming industry. Economically significant coronaviruses of farm animals include porcine coronavirus (transmissible gastroenteritis coronavirus, TGE) and bovine coronavirus, which both result in diarrhea in young animals. Feline Coronavirus: two forms, Feline enteric coronavirus is a pathogen of minor clinical significance, but spontaneous mutation of this virus can result in feline infectious peritonitis (FIP), a disease associated with high mortality. There are two types of canine coronavirus (CCoV), one that causes mild gastrointestinal disease and one that has been found to cause respiratory disease. Mouse hepatitis virus (MHV) is a coronavirus that causes an epidemic murine illness with high mortality, especially among colonies of laboratory mice. Prior to the discovery of SARS-CoV, MHV had been the best-studied coronavirus both in vivo and in vitro as well as at the molecular level. Some strains of MHV cause a progressive demyelinating encephalitis in mice which has been used as a murine model for multiple sclerosis. Significant research efforts have been focused on elucidating the viral pathogenesis of these animal coronaviruses, especially by virologists interested in veterinary and zoonotic diseases.
Replication of Coronavirus begins with entry to the cell which takes place in the cytoplasm in a membrane-protected microenvironment. Upon entry to the cell the virus particle is uncoated and the RNA genome is deposited into the cytoplasm. The Coronavirus genome has a 5’ methylated cap and a 3’polyadenylated tail. This also allows the RNA to attach to ribosomes for translation. Coronaviruses also have a protein known as a replicase encoded in its genome which allows the RNA viral genome to be transcribed into new RNA copies using the host cells machinery. The replicase is the first protein to be made as once the gene encoding the replicase is translated the translation is stopped by a stop codon. This is known as a nested transcript, where the transcript only encodes one gene—it is monocistronic. The RNA genome is replicated and a long polyprotein is formed, where all of the proteins are attached. Coronaviruses have a non-structural protein called a protease which is able to separate the proteins in the chain. This is a form of genetic economy for the virus allowing it to encode the greatest number of genes in a small number of nucleotides.
Coronavirus transcription involves a discontinuous RNA synthesis (template switch) during the extension of a negative copy of the subgenomic mRNAs. Basepairing during transcription is a requirement. Coronavirus N protein is required for coronavirus RNA synthesis, and has RNA chaperone activity that may be involved in template switch. Both viral and cellular proteins are required for replication and transcription. Coronaviruses initiate translation by cap-dependent and cap-independent mechanisms. Cell macromolecular synthesis may be controlled after Coronavirus infection by locating some virus proteins in the host cell nucleus. Infection by different coronaviruses cause in the host alteration in the transcription and translation patterns, in the cell cycle, the cytoskeleton, apoptosis and coagulation pathways, inflammation, and immune and stress responses.
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 issued a press release stating that a novel coronavirus identified by a number of laboratories was the causative agent for SARS. The virus was officially named the SARS coronavirus (SARS-CoV).
The epidemic resulted in over 8,000 infections, about 10% of which resulted in death. X-ray crystallography studies performed at the Advanced Light Source of Lawrence Berkeley National Laboratory have begun to give hope of a vaccine against the disease "since [the spike protein] appears to be recognized by the immune system of the host."
Following the high-profile publicity of SARS outbreaks, there has been a renewed interest in coronaviruses among virologists. For many years, scientists knew about only two human coronaviruses (HCoV-229E and HCoV-OC43). The discovery of SARS-CoV added a third human coronavirus.
By the end of 2004, three independent research labs reported the discovery of a fourth human coronavirus. It has been named NL63, NL, and the New Haven coronavirus by different research groups. The three labs are still arguing over which one discovered the virus first and has the right to name it.
In September 2012, what is believed to be a sixth new type of coronavirus, tentatively referred to as Novel Coronavirus 2012, being like SARS (but still distinct from it and from the common-cold coronavirus) was discovered in Qatar and Saudi Arabia. The World Health Organisation has accordingly issued a global alert and an interim case definition to help countries to strengthen health protection measures against it. The WHO update on 28 September 2012 said that the virus did not seem to pass easily from person to person. However, on May 12, 2013, a case of contamination from human to human in France was confirmed by the French Ministry of Social Affairs and Health. In addition, cases of person-to-person transmission have been reported by the Ministry of Health in Tunisia. Two confirmed cases seem to have caught the disease from their late father, who became ill after a visit to Qatar and Saudi Arabia. On Oct. 30 2013, Oman officials announced the first case in this sultanate. So far (as of Oct. 30 2013), there have been one hundred and twenty four cases and fifty two deaths in Saudi Arabia. After the Dutch Erasmus Medical Centre sequenced the virus, the virus was given a new name, Human Corona Virus-Erasmus Medical Centre (HCoV-EMC). The final name for the virus is: Middle East respiratory syndrome coronavirus (MERS-CoV).
Coronaviruses have been recognized as causing pathological conditions in veterinary medicine since the early 1970s. Except for avian infectious bronchitis, the major related diseases have mainly an intestinal location.
(listed following their estimated economical importance)
The most recent common ancestor of the coronovirus has been placed at 10,000 years before the present. They may be considerably older than this.
Another estimate places the most recent common ancestor (MRCA) of all coronaviruses ~8100 BC. The MRCA of Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus have been placed at ~2400 BC, ~3300 BC, ~2800 BC and ~3000 BC, respectively. It appears that bats and birds, the warm blooded flying vertebrates, are ideal hosts for the coronavirus gene source with bats for Alphacoronavirus and Betacoronavirus and birds for Gammacoronavirus and Deltacoronavirus, to fuel coronavirus evolution and dissemination.
Bovine coronavirus and canine respiratory coronavirus diverged from a common ancestor in 1951. Bovine coronavirus and human coronavirus OC43 diverged in 1899. Bovine coronavirus diverged from the equine coronavirus species at the end of the 18th century.
Another estimate suggests that human coronavirus OC43 diverged from bovine coronavirus in 1890.
The MRCA of human coronavirus OC43 has been dated to the 1950s.
Middle East respiratory syndrome coronavirus although related to several bat species appears to have diverged from these several centuries ago.
The most closely related bat coronovirus and the SARS coronavirus diverged in 1986.
A path of evolution of the SARS virus has been proposed. The authors suggest that the ancestors of this virus first infected the species of the genus Hipposideridae, subsequently spread to species of the Rhinolophidae and then to civets and finally to humans.
Alpaca coronavirus and human coronavirus 229E diverged before 1960.
The human coronavirus NL63 and a bat coronovirus shared an MRCA 563 to 822 years ago.