Coxsackievirus
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Coxsackieviruses are a few related
enterovirus ''Enterovirus'' is a genus of positive-sense single-stranded RNA viruses associated with several human and mammalian diseases. Enteroviruses are named by their transmission-route through the intestine ('enteric' meaning intestinal). Serologic ...
es that belong to the ''
Picornaviridae Picornaviruses are a group of related nonenveloped RNA viruses which infect vertebrates including fish, mammals, and birds. They are viruses that represent a large family of small, positive-sense, single-stranded RNA viruses with a 30 nm ...
'' family of
nonenveloped A viral envelope is the outermost layer of many types of viruses. It protects the genetic material in their life cycle when traveling between host cells. Not all viruses have envelopes. A viral envelope protein or E protein is a protein in the env ...
, linear,
positive-sense single-stranded 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 i ...
es, as well as its genus ''Enterovirus'', which also includes
poliovirus Poliovirus, the causative agent of polio (also known as poliomyelitis), is a serotype of the species '' Enterovirus C'', in the family of '' Picornaviridae''. There are three poliovirus serotypes, numbered 1, 2, and 3. Poliovirus is composed ...
and echovirus. Enteroviruses are among the most common and important human pathogens, and ordinarily its members are transmitted by the
fecal–oral route The fecal–oral route (also called the oral–fecal route or orofecal route) describes a particular route of transmission of a disease wherein pathogens in fecal particles pass from one person to the mouth of another person. Main causes of fec ...
. Coxsackieviruses share many characteristics with poliovirus. With control of poliovirus infections in much of the world, more attention has been focused on understanding the nonpolio enteroviruses such as coxsackievirus. Coxsackieviruses are among the leading causes of aseptic meningitis (the other usual suspects being echovirus and mumps virus). The entry of coxsackievirus into cells, especially endothelial cells, is mediated by coxsackievirus and adenovirus receptor.


Groups

Coxsackieviruses are divided into
group A Group A is a set of motorsport regulations administered by the FIA covering production derived touring cars for competition, usually in touring car racing and rallying. In contrast to the short-lived Group B and Group C, Group A vehicles wer ...
and
group B Group B was a set of regulations for Grand tourer, grand touring (GT) cars used in sports car racing and rallying introduced in 1982 by the Fédération Internationale de l'Automobile (FIA). Although permitted to enter a GT class of the World S ...
viruses based on early observations of their pathogenicity in neonatal mice. Group A coxsackieviruses were noted to cause a
flaccid paralysis Flaccid paralysis is a neurological condition characterized by weakness or paralysis and reduced muscle tone without other obvious cause (e.g., trauma). This abnormal condition may be caused by disease or by trauma affecting the nerves associ ...
(which was caused by generalized myositis) while group B coxsackieviruses were noted to cause a spastic paralysis (due to focal muscle injury and degeneration of neuronal tissue). At least 23
serotype A serotype or serovar is a distinct variation within a species of bacteria or virus or among immune cells of different individuals. These microorganisms, viruses, or Cell (biology), cells are classified together based on their shared reactivity ...
s (1–22, 24) of group A and six serotypes (1–6) of group B are recognized.


A

In general, group A coxsackieviruses tend to infect the skin and mucous membranes, causing herpangina; acute hemorrhagic
conjunctivitis Conjunctivitis, also known as pink eye or Madras eye, is inflammation of the conjunctiva, the thin, clear layer that covers the white surface of the eye and the inner eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness ...
; and
hand, foot, and mouth disease Hand, foot, and mouth disease (HFMD) is a common infection caused by a group of enteroviruses. It typically begins with a fever and feeling generally unwell. This is followed a day or two later by flat discolored spots or bumps that may blis ...
. Both group A and group B coxsackieviruses can cause nonspecific febrile illnesses,
rash A rash is a change of the skin that affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracke ...
es, upper respiratory tract disease, and aseptic meningitis. The
basic reproduction number In epidemiology, the basic reproduction number, or basic reproductive number (sometimes called basic reproduction ratio or basic reproductive rate), denoted R_0 (pronounced ''R nought'' or ''R zero''), of an infection is the expected number ...
(R0) for Coxsackievirus A16 (Cox A16) was estimated to a median of 2.50 with an interquartile range of 1.96 to 3.67.


B

Group B coxsackieviruses tend to infect the heart, pleura, pancreas, and liver, causing pleurodynia,
myocarditis Myocarditis is inflammation of the cardiac muscle. Myocarditis can progress to inflammatory cardiomyopathy when there is associated ventricular remodeling and cardiac dysfunction due to chronic inflammation. Symptoms can include shortness of bre ...
,
pericarditis Pericarditis () is inflammation of the pericardium, the fibrous sac surrounding the heart. Symptoms typically include sudden onset of sharp chest pain, which may also be felt in the shoulders, neck, or back. The pain is typically less severe whe ...
, and
hepatitis Hepatitis is inflammation of the liver parenchyma, liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), Anorexia (symptom), poor appetite ...
(inflammation of the liver not related to the hepatotropic viruses). Coxsackie B infection of the heart can lead to
pericardial effusion A pericardial effusion is an abnormal accumulation of fluid in the pericardial cavity. The pericardium is a two-part membrane surrounding the heart: the outer fibrous Connective tissue, connective membrane and an inner two-layered serous membrane ...
. The development of insulin-dependent diabetes has recently been associated with recent enteroviral infection, particularly coxsackievirus B
pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormone A hormone (from the Ancient Greek, Greek participle , "se ...
. This relationship is currently being studied further.
Sjögren syndrome Sjögren is a Swedish surname. Notable people with the surname include: * Anders Johan Sjögren (1794–1855), Finnish linguist, historian, ethnographer and explorer * Ann Mari Sjögren, Swedish fantasy artist and illustrator * Christer Sjögren, ...
is also being studied in connection with coxsackievirus, .


Taxonomy

There were 29 species of coxsackieviruses until 1999, when two of them were abolished and the rest merged into other species.ICTV 7th Report van Regenmortel, M.H.V., Fauquet, C.M., Bishop, D.H.L., Carstens, E.B., Estes, M.K., Lemon, S.M., Maniloff, J., Mayo, M.A., McGeoch, D.J., Pringle, C.R. and Wickner, R.B. (2000). Virus taxonomy. Seventh report of the International Committee on Taxonomy of Viruses. Academic Press, San Diego. 1162 pp. https://ictv.global/ictv/proposals/ICTV%207th%20Report.pd

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History

The coxsackieviruses were discovered in 1948–49 by Gilbert Dalldorf, a scientist working at the New York State Department of Health in
Albany, New York Albany ( ) is the List of capitals in the United States, capital city of the U.S. state of New York (state), New York. It is located on the west bank of the Hudson River, about south of its confluence with the Mohawk River. Albany is the oldes ...
. Dalldorf, in collaboration with Grace Sickles, had been searching for a cure for
poliomyelitis Poliomyelitis ( ), commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 75% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe ...
. Earlier work Dalldorf had done in monkeys suggested that fluid collected from a nonpolio virus preparation could protect against the crippling effects of polio. Using newborn mice as a vehicle, Dalldorf attempted to isolate such protective viruses from the feces of polio patients. In carrying out these experiments, he discovered viruses that often mimicked mild or nonparalytic polio. The virus family he discovered was eventually given the name Coxsackie, from
Coxsackie, New York Coxsackie ( ) is a town in Greene County, New York, United States. The population in the 2020 census was 8,382, a decrease from the 2010 census. It is the second-largest town in Greene County after Catskill. The name of the town is said to be ...
, a small town on the Hudson River where Dalldorf had obtained the first fecal specimens. Dalldorf also collaborated with Gifford on many early papers. The coxsackieviruses subsequently were found to cause a variety of infections, including epidemic pleurodynia ( Bornholm disease), and were subdivided into groups A and B based on their pathology in newborn mice. (Coxsackie A virus causes paralysis and death of the mice, with extensive skeletal muscle necrosis; Coxsackie B causes less severe infection in the mice, but with damage to more organ systems, such as heart, brain, liver, pancreas, and skeletal muscles.) The use of suckling mice was not Dalldorf's idea but was brought to his attention in a paper written by Danish scientists Orskov and Andersen in 1947, who were using such mice to study a mouse virus. The discovery of the coxsackieviruses stimulated many virologists to use this system, and ultimately resulted in the isolation of a large number of so-called "enteric" viruses from the gastrointestinal tract that were unrelated to poliovirus, and some of which were oncogenic (cancer-causing). The discovery of the coxsackieviruses yielded further evidence that viruses can sometimes interfere with each other's growth and replication within a host animal. Other researchers found this interference can be mediated by a substance produced by the host animal, a protein now known as
interferon Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten ...
. Interferon has since become prominent in the treatment of a variety of cancers and infectious diseases. In 2007, an outbreak of coxsackievirus occurred in eastern China. It has been reported that 22 children died. More than 800 people were affected, with 200 children hospitalized. Cavatak, a wild-type Coxsackievirus A21, is being used in human clinical trials as an oncolytic virus. SCAR-Fc (Soluble Receptor Analogue) is an experimental prophylactic treatment against coxsackievirus B3 (CVB) infections.


References


External links


3D macromolecular structures of Coxsackieviruses from the EM Data Bank(EMDB)
{{Diseases of the skin and appendages by morphology Enteroviruses Unaccepted virus taxa Polyphyletic groups