Coxsackievirus

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Coxsackie B4 virus Coxsackie B4 virus.JPG
Coxsackie B4 virus

Coxsackieviruses are a few related enteroviruses that belong to the Picornaviridae family of nonenveloped, linear, positive-sense single-stranded RNA viruses, as well as its genus Enterovirus, which also includes poliovirus and echovirus. Enteroviruses are among the most common and important human pathogens, and ordinarily its members are transmitted by the fecal–oral route. 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.

Contents

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 and group B viruses based on early observations of their pathogenicity in neonatal mice. [1] Group A coxsackieviruses were noted to cause a flaccid paralysis (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 serotypes (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; and hand, foot, and mouth disease. [2]

Both group A and group B coxsackieviruses can cause nonspecific febrile illnesses, rashes, upper respiratory tract disease, and aseptic meningitis.

The basic reproduction 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. [3]

B

Group B coxsackieviruses tend to infect the heart, pleura, pancreas, and liver, causing pleurodynia, myocarditis, pericarditis, and hepatitis (inflammation of the liver not related to the hepatotropic viruses). Coxsackie B infection of the heart can lead to pericardial effusion.

The development of insulin-dependent diabetes has recently been associated with recent enteroviral infection, particularly coxsackievirus B pancreatitis. This relationship is currently being studied further.

Sjögren syndrome is also being studied in connection with coxsackievirus, as of January 2010. [4]

Taxonomy

There were 29 species of coxsackieviruses until 1999, when two of them were abolished and the rest merged into other species. [5]

Former nameCurrent name [5]
Human coxsackievirus A1 Enterovirus C [6]
Human coxsackievirus A2 Enterovirus A [7]
Human coxsackievirus A3 Enterovirus A [7]
Human coxsackievirus A4 abolished [8]
Human coxsackievirus A5 Enterovirus A [7]
Human coxsackievirus A6 abolished [9]
Human coxsackievirus A7 Enterovirus A [7]
Human coxsackievirus A8 Enterovirus A [7]
Human coxsackievirus A9 Enterovirus B [10]
Human coxsackievirus A10 Enterovirus A [7]
Human coxsackievirus A11 Enterovirus C [6]
Human coxsackievirus A12 Enterovirus A [7]
Human coxsackievirus A13 Enterovirus C [6]
Human coxsackievirus A14 Enterovirus A [7]
Human coxsackievirus A15 Enterovirus C [6]
Human coxsackievirus A16 Enterovirus A [7]
Human coxsackievirus A17 Enterovirus C [6]
Human coxsackievirus A18 Enterovirus C [6]
Human coxsackievirus A19 Enterovirus C [6]
Human coxsackievirus A20 Enterovirus C [6]
Human coxsackievirus A21 Enterovirus C [6]
Human coxsackievirus A22 Enterovirus C [6]
Human coxsackievirus A24 Enterovirus C [6]
Human coxsackievirus B1 Enterovirus B [10]
Human coxsackievirus B2 Enterovirus B [10]
Human coxsackievirus B3 Enterovirus B [10]
Human coxsackievirus B4 Enterovirus B [10]
Human coxsackievirus B5 Enterovirus B [10]
Human coxsackievirus B6 Enterovirus B [10]

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.

Dalldorf, in collaboration with Grace Sickles, [11] [12] had been searching for a cure for poliomyelitis. 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, a small town on the Hudson River where Dalldorf had obtained the first fecal specimens. [13]

Dalldorf also collaborated with Gifford on many early papers. [14] [15] [16] [17]

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. 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. [18]

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. [19]

Related Research Articles

<span class="mw-page-title-main">Coxsackie A virus</span> Virus that causes digestive upset and sometimes heart damage

Coxsackie A virus (CAV) is a cytolytic Coxsackievirus of the Picornaviridae family, an enterovirus.

<span class="mw-page-title-main">Bornholm disease</span> Medical condition

Bornholm disease, also known as epidemic pleurodynia, is a condition characterized by myositis of the abdomen or chest caused by the Coxsackie B virus or other viruses. The myositis manifests as an intermittent stabbing pain in the musculature that is seen primarily in children and young adults.

<span class="mw-page-title-main">Rhinovirus</span> Genus of viruses (Enterovirus)

The rhinovirus is a positive-sense, single-stranded RNA virus belonging to the genus Enterovirus in the family Picornaviridae. Rhinovirus is the most common viral infectious agent in humans and is the predominant cause of the common cold.

<span class="mw-page-title-main">Hand, foot, and mouth disease</span> Common human disease caused by a group of viruses

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 blister, on the hands, feet and mouth and occasionally buttocks and groin. Signs and symptoms normally appear 3–6 days after exposure to the virus. The rash generally resolves on its own in about a week. Fingernail and toenail loss may occur a few weeks later, but they will regrow with time.

Coxsackie B4 virus are enteroviruses that belong to the Picornaviridae family. These viruses can be found worldwide. They are positive-sense, single-stranded, non-enveloped RNA viruses with icosahedral geometry. Coxsackieviruses have two groups, A and B, each associated with different diseases. Coxsackievirus group A is known for causing hand-foot-and-mouth diseases while Group B, which contains six serotypes, can cause a varying range of symptoms like gastrointestinal distress myocarditis. Coxsackievirus B4 has a cell tropism for natural killer cells and pancreatic islet cells. Infection can lead to beta cell apoptosis which increases the risk of insulitis.

<span class="mw-page-title-main">Coxsackie B virus</span> Virus that causes digestive upset and sometimes heart damage

Coxsackie B is a group of six serotypes of coxsackievirus (CVB1-CVB6), a pathogenic enterovirus, that trigger illness ranging from gastrointestinal distress to full-fledged pericarditis and myocarditis.

<span class="mw-page-title-main">Poliovirus</span> Enterovirus

Poliovirus, the causative agent of polio, is a serotype of the species Enterovirus C, in the family of Picornaviridae. There are three poliovirus serotypes: types 1, 2, and 3.

<span class="mw-page-title-main">Picornavirus</span> Family of viruses

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 icosahedral capsid. The viruses in this family can cause a range of diseases including the common cold, poliomyelitis, meningitis, hepatitis, and paralysis.

<i>Enterovirus</i> Genus of viruses

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.

<span class="mw-page-title-main">Decay-accelerating factor</span> Mammalian protein found in Homo sapiens

Complement decay-accelerating factor, also known as CD55 or DAF, is a protein that, in humans, is encoded by the CD55 gene.

<span class="mw-page-title-main">Pleconaril</span> Antiviral drug

Pleconaril (Picovir) is an antiviral drug that was being developed by Schering-Plough for prevention of asthma exacerbations and common cold symptoms in patients exposed to picornavirus respiratory infections. Pleconaril, administered either orally or intranasally, is active against viruses in the Picornaviridae family, including Enterovirus and Rhinovirus. It has shown useful activity against the dangerous enterovirus D68.

<span class="mw-page-title-main">Vincent Racaniello</span> American biologist

Vincent R. Racaniello is a Higgins Professor in the Department of Microbiology and Immunology at Columbia University's College of Physicians and Surgeons. He is a co-author of a textbook on virology, Principles of Virology.

<span class="mw-page-title-main">Enterovirus 71</span> Species of virus

Enterovirus 71 (EV71), also known as Enterovirus A71 (EV-A71), is a virus of the genus Enterovirus in the Picornaviridae family, notable for its role in causing epidemics of severe neurological disease and hand, foot, and mouth disease in children. It was first isolated and characterized from cases of neurological disease in California in 1969. Enterovirus 71 infrequently causes polio-like syndrome permanent paralysis.

sCAR-Fc is an experimental prophylactic treatment against coxsackievirus B3 (CVB) infections. Coxsackievirus B3 can cause cardiac damage, eventually resulting in a weakened and enlarged heart that is termed dilated cardiomyopathy. While many other treatments inhibit viral proliferation in myocytes, sCAR-Fc prevents the virus entering the cell by competitively binding to coxsackie virus and adenovirus receptors (CAR) on the membrane of myocytes.

<span class="mw-page-title-main">Acute hemorrhagic conjunctivitis</span> Medical condition

Acute hemorrhagic conjunctivitis (AHC) is a derivative of the highly contagious conjunctivitis virus, otherwise known as pink eye. Symptoms include excessively red, swollen eyes as well as subconjunctival hemorrhaging. Currently, there is no known treatment and patients are required to merely endure the symptoms while the virus runs its five- to seven-day course. While it was first identified in Ghana, the virus has now been seen in China, India, Egypt, Cuba, Singapore, Taiwan, Japan, Pakistan, Thailand, and the United States.

<i>Enterovirus C</i> Species of virus

Enterovirus C is a species of enterovirus. Its best known subtype is poliovirus, the cause of poliomyelitis. There are three serotypes of poliovirus, PV1, PV2, and PV3. Other subtypes of Enterovirus C include EV-C95, EV-C96, EV-C99, EV-C102, EV-C104, EV-C105, EV-C109, EV-C116, EV-C117, and EV-C118. Some non-polio types of Enterovirus C have been associated with the polio-like condition AFP, including 2 isolates of EV-C95 from Chad.

<span class="mw-page-title-main">Enterovirus 68</span> Species of virus

Enterovirus D68 (EV-D68) is a member of the Picornaviridae family, an enterovirus. First isolated in California in 1962 and once considered rare, it has been on a worldwide upswing in the 21st century. It is suspected of causing a polio-like disorder called acute flaccid myelitis (AFM).

Echovirus 9 is a serotype of echovirus. When first discovered, it was labelled as a coxsackie A virus, A23. It was later discovered that A23 was an echovirus antigenically identical to the already-known echovirus 9.

<span class="mw-page-title-main">Acute flaccid myelitis</span> Condition of the spinal cord with symptoms of rapid onset of arm or leg weakness

Acute flaccid myelitis (AFM) is a serious condition of the spinal cord. Symptoms include rapid onset of arm or leg weakness and decreased reflexes. Difficulty moving the eyes, speaking, or swallowing may also occur. Occasionally, numbness or pain may be present. Complications can include trouble breathing.

The 1997 Sarawak HFMD outbreak is a hand, foot, and mouth disease (HFMD) outbreak from April until June caused by the Enterovirus 71 (EV-71) affecting 600 children in the state of Sarawak in Malaysia. Sarawak is the first state in Malaysia that reported HFMD outbreak. An estimated 28 to 31 of the infected children died as a result. The affected children are aged between five months to six years.

References

  1. ↑ Pedro-Pons, Agustín (1968). Patología y Clínica Médicas (in Spanish). Vol. 6 (3rd ed.). Barcelona: Salvat. p. 598. ISBN   978-84-345-1106-4.
  2. ↑ Seitsonen, Jani; Shakeel, Shabih; Susi, Petri; Pandurangan, Arun P.; Sinkovits, Robert S.; Hyvönen, Heini; Laurinmäki, Pasi; Ylä-Pelto, Jani; Topf, Maya; Hyypiä, Timo; Butcher, Sarah J. (2012). "Structural analysis of coxsackievirus A7 reveals conformational changes associated with uncoating". Journal of Virology. 86 (13): 7207–7215. doi:10.1128/JVI.06425-11. PMC   3416324 . PMID   22514349.
  3. ↑ Ma E, Fung C, Yip SH, Wong C, Chuang SK, Tsang T (Aug 2011). "Estimation of the basic reproduction number of enterovirus 71 and coxsackievirus A16 in hand, foot, and mouth disease outbreaks". Pediatr Infect Dis J. 30 (8): 675–9. doi:10.1097/INF.0b013e3182116e95. PMID   21326133. S2CID   25977037.
  4. ↑ Triantafyllopoulou, Antigoni; Tapinos, Nikos; Moutsopoulos, Haralampos; et al. (2004). "Evidence for Coxsackievirus Infection in Primary Sjogren's Syndrome". Arthritis & Rheumatism. 50 (9): 2897–2902. doi: 10.1002/art.20463 . PMID   15457458.
  5. 1 2 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.pdf
  6. 1 2 3 4 5 6 7 8 9 10 11 "ICTV Taxonomy history: Enterovirus C". International Committee on Taxonomy of Viruses (ICTV). Retrieved 6 February 2020.
  7. 1 2 3 4 5 6 7 8 9 "ICTV Taxonomy history: Enterovirus A". International Committee on Taxonomy of Viruses (ICTV). Archived from the original on 6 February 2020. Retrieved 6 February 2020.
  8. ↑ "ICTV Taxonomy history: Human coxsackievirus A4". International Committee on Taxonomy of Viruses (ICTV). Retrieved 6 February 2020.
  9. ↑ "ICTV Taxonomy history: Human coxsackievirus A6". International Committee on Taxonomy of Viruses (ICTV). Retrieved 6 February 2020.
  10. 1 2 3 4 5 6 7 "ICTV Taxonomy history: Enterovirus B". International Committee on Taxonomy of Viruses (ICTV). Retrieved 6 February 2020.
  11. ↑ Dalldorf G, Sickles GM (July 1948). "An Unidentified, Filtrable Agent Isolated From the Feces of Children With Paralysis". Science. 108 (2794): 61–62. Bibcode:1948Sci...108...61D. doi:10.1126/science.108.2794.61. PMID   17777513.
  12. ↑ DALLDORF G, SICKLES GM (June 1949). "A virus recovered from the feces of poliomyelitis patients pathogenic for suckling mice". J. Exp. Med. 89 (6): 567–82. doi:10.1084/jem.89.6.567. PMC   2135891 . PMID   18144319.
  13. ↑ Coxsackie NY and the virus named after it Archived 2017-05-28 at the Wayback Machine posted to Virology Blog 10 AUGUST 2009 by Professor Vincent Racaniello. Accessed via internet August 20, 2012.
  14. ↑ Dalldorf G, Gifford R (June 1951). "Clinical and epidemiologic observations of Coxsackie-virus infection". N. Engl. J. Med. 244 (23): 868–73. doi:10.1056/NEJM195106072442302. PMID   14843332.
  15. ↑ Dalldorf G, Gifford R (November 1952). "Adaptation of Group B Coxsackie virus to adult mouse pancreas". J. Exp. Med. 96 (5): 491–7. doi:10.1084/jem.96.5.491. PMC   2136156 . PMID   13000059.
  16. ↑ Dalldorf G, Gifford R (January 1954). "Susceptibility of gravid mice to Coxsackie virus infection". J. Exp. Med. 99 (1): 21–7. doi:10.1084/jem.99.1.21. PMC   2136322 . PMID   13118060.
  17. ↑ DALLDORF G, GIFFORD R (February 1955). "Recognition of mouse ectromelia". Proc. Soc. Exp. Biol. Med. 88 (2): 290–2. doi:10.3181/00379727-88-21566. PMID   14357417. S2CID   19245364.
  18. ↑ "China says it controls viral outbreak in children". Reuters. 2007-05-19..
  19. ↑ Werk D, Pinkert S, Heim A, et al. (September 2009). "Combination of soluble coxsackievirus-adenovirus receptor and anti-coxsackievirus siRNAs exerts synergistic antiviral activity against coxsackievirus B3". Antiviral Res. 83 (3): 298–306. doi:10.1016/j.antiviral.2009.07.002. PMID   19591879.
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