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''Human coronavirus HKU1'' (''HCoV-HKU1'') is a species of
coronavirus 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 co ...
in humans and animals. It causes an upper respiratory disease with symptoms of the
common cold The common cold or the cold is a viral infectious disease of the upper respiratory tract that primarily affects the respiratory mucosa of the nose, throat, sinuses, and larynx. Signs and symptoms may appear fewer than two days after expos ...
, but can advance to
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 severit ...
and bronchiolitis. It was first discovered in January 2004 from one man in
Hong Kong Hong Kong ( (US) or (UK); , ), officially the Hong Kong Special Administrative Region of the People's Republic of China (abbr. Hong Kong SAR or HKSAR), is a List of cities in China, city and Special administrative regions of China, special ...
. Subsequent research revealed it has global distribution and earlier genesis. The virus is an enveloped, positive-sense,
single-stranded When referring to DNA transcription, the coding strand (or informational strand) is the DNA strand whose base sequence is identical to the base sequence of the RNA transcript produced (although with thymine replaced by uracil). It is this stra ...
RNA virus An RNA virus is a virusother than a retrovirusthat has ribonucleic acid ( RNA) as its genetic material. The nucleic acid is usually single-stranded RNA (ssRNA) but it may be double-stranded (dsRNA). Notable human diseases caused by RNA virus ...
which enters its host cell by binding to the N-acetyl-9-O-acetylneuraminic acid receptor. It has the
Hemagglutinin esterase Hemagglutinin esterase (HEs) is a glycoprotein that certain enveloped viruses possess and use as an invading mechanism. HEs helps in the attachment and destruction of certain sialic acid receptors that are found on the host cell surface. V ...
(HE) gene, which distinguishes it as a member of the genus ''
Betacoronavirus ''Betacoronavirus'' (β-CoVs or Beta-CoVs) is one of four genera (''Alpha''-, ''Beta-'', '' Gamma-'', and '' Delta-'') of coronaviruses. Member viruses are enveloped, positive-strand RNA viruses that infect mammals (of which humans are part). ...
'' and subgenus ''
Embecovirus ''Embecovirus'' is a subgenus of coronaviruses in the genus ''Betacoronavirus''. The viruses in this subgenus, unlike other coronaviruses, have a hemagglutinin esterase (HE) gene. The viruses in the subgenus were previously known as group 2a coro ...
''.


History

HCoV-HKU1 was first detected in January 2004, in a 71-year-old man who was hospitalized due to
acute respiratory distress syndrome Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin colo ...
and radiographically confirmed
bilateral pneumonia Pneumonia can be classified in several ways, most commonly by where it was acquired (hospital versus community), but may also by the area of lung affected or by the causative organism. There is also a combined clinical classification, which combi ...
. The man had recently returned to Hong Kong from
Shenzhen, China Shenzhen (; ; ; ), also historically known as Sham Chun, is a major sub-provincial city and one of the special economic zones of China. The city is located on the east bank of the Pearl River estuary on the central coast of southern provi ...
.


Virology

Woo and coworkers were unsuccessful in their attempts to grow a HCoV-HKU1 isolate but were able to obtain the complete genomic sequence.
Phylogenetic analysis In biology, phylogenetics (; from Greek φυλή/ φῦλον [] "tribe, clan, race", and wikt:γενετικός, γενετικός [] "origin, source, birth") is the study of the evolutionary history and relationships among or within groups o ...
showed that HKU1 is most closely related to the mouse hepatitis virus (MHV), and is distinct in that regard from other known human
betacoronaviruses ''Betacoronavirus'' (β-CoVs or Beta-CoVs) is one of four genera (''Alpha''-, ''Beta-'', '' Gamma-'', and '' Delta-'') of coronaviruses. Member viruses are enveloped, positive-strand RNA viruses that infect mammals (of which humans are part). ...
, such as
HCoV-OC43 Human coronavirus OC43 (HCoV-OC43) is a member of the species ''Betacoronavirus 1'', which infects humans and cattle. The infecting coronavirus is an enveloped, positive-sense, single-stranded RNA virus that enters its host cell by binding to t ...
. When the
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), spike (S), and
nucleocapsid A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may ...
(N) genes were analyzed, incompatible phylogenetic relationships were discovered. Complete genome sequencing of 22 strains of HCoV-HKU1 confirmed this was due to natural recombination. HCoV-HKU1 likely originated from
rodent Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia (), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are n ...
s. HCoV-HKU1 is one of seven known coronaviruses to infect humans. The other six are: * Human coronavirus 229E (HCoV-229E) * Human coronavirus NL63 (HCoV-NL63) * Human coronavirus OC43 (HCoV-OC43) * Middle East respiratory syndrome-related coronavirus (MERS-CoV) * Severe acute respiratory syndrome coronavirus (SARS-CoV-1) * Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) The structures of HCoV-HKU1 spike (S) and
hemagglutinin esterase Hemagglutinin esterase (HEs) is a glycoprotein that certain enveloped viruses possess and use as an invading mechanism. HEs helps in the attachment and destruction of certain sialic acid receptors that are found on the host cell surface. V ...
(HE) proteins have been resolved by
Cryo-EM Cryogenic electron microscopy (cryo-EM) is a cryomicroscopy technique applied on samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An aqueous sample so ...
in 2016 and 2020, respectively. The S protein () has been noted for its large size. The HE protein () differs from conventional ones (such as the one in OC43) by having a much smaller vestigial
lectin Lectins are carbohydrate-binding proteins that are highly specific for sugar groups that are part of other molecules, so cause agglutination of particular cells or precipitation of glycoconjugates and polysaccharides. Lectins have a role in rec ...
domain. This domain is shielded from recognition by the immune system via size changes and glycosylation.


Epidemiology

A trace-back analysis of SARS negative nasopharyngeal aspirates from patients with respiratory illness during the SARS period in 2003, identified the presence of CoV-HKU1 RNA in the sample from a 35-year-old woman with pneumonia. Following the initial reports of the discovery of HCoV-HKU1, the virus was identified that same year in 10 patients in
northern Australia The unofficial geographic term Northern Australia includes those parts of Queensland and Western Australia north of latitude 26° and all of the Northern Territory. Those local government areas of Western Australia and Queensland that lie p ...
. Respiratory samples were collected between May and August (winter in Australia). Investigators found that most of the HCoV-HKU1–positive samples originated from children in the later winter months. The first known cases in the Western hemisphere were discovered in 2005 after analysing older specimens by clinical virologists at
Yale-New Haven Hospital Yale New Haven Hospital (YNHH) is a 1,541-bed hospital located in New Haven, Connecticut. It is owned and operated by the Yale New Haven Health System. YNHH includes the 168-bed Smilow Cancer Hospital at Yale New Haven, the 201-bed Yale New Ha ...
in
New Haven, Connecticut New Haven is a city in the U.S. state of Connecticut. It is located on New Haven Harbor on the northern shore of Long Island Sound in New Haven County, Connecticut and is part of the New York City metropolitan area. With a population of 134 ...
who were curious to discover if HCoV-HKU1 was in their area. They conducted a study of specimens collected in a 7-week period (December 2001 – February 2002) in 851 infants and children. Specimens of nine children had human coronavirus HKU1. These children had respiratory tract infections at the time the specimens were collected (in one girl so severe that mechanical ventilation was needed), while testing negative for other causes like Human respiratory syncytial virus (RSV), parainfluenza viruses (types 1–3), influenza A and B viruses, and
adenovirus Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from ...
by direct immunofluorescence assay as well as
human metapneumovirus ''Human metapneumovirus'' (HMPV) is a negative-sense single-stranded RNA virus of the family ''Pneumoviridae'' and is closely related to the '' Avian metapneumovirus'' (AMPV) subgroup C. It was isolated for the first time in 2001 in the Netherlan ...
and HCoV-NH by
reverse transcription polymerase chain reaction Reverse transcription polymerase chain reaction (RT-PCR) is a laboratory technique combining reverse transcription of RNA into DNA (in this context called complementary DNA or cDNA) and amplification of specific DNA targets using polymerase ch ...
(RT-PCR). The researchers reported that the strains identified in New Haven were similar to the strain found in Hong Kong and suggested a worldwide distribution. These strains found in New Haven is not to be confused with ''HCoV-NH'' (New Haven coronavirus), which is a strain of Human coronavirus NL63. In July 2005, six cases were reported in France. In these cases, French investigators utilized improved techniques for recovering the virus from nasopharyngeal aspirates and from stool samples.


See also

*
Tylonycteris bat coronavirus HKU4 ''Tylonycteris bat coronavirus HKU4'' (''Bat-CoV HKU4'') is an enveloped, positive-sense single-stranded RNA virus mammalian Group 2 ''Betacoronavirus'' that has been found to be genetically related to the '' Middle East respiratory syndrome-rela ...
*
Rousettus bat coronavirus HKU9 ''Rousettus bat coronavirus HKU9'' (''HKU9-1'') is an enveloped, positive-sense, single-stranded RNA mammalian Group 2 ''Betacoronavirus'' discovered in ''Rousettus'' bats in China in 2011. This strain of coronavirus is closely related to the EM ...


References


External links

* {{Taxonbar, from=Q16983360 Betacoronaviruses