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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.

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. 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.

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.

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.

Taxonomy

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

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, 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.

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. 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

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. ^ 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. ^ "ICTV Taxonomy history: Enterovirus C". International Committee on Taxonomy of Viruses (ICTV). Retrieved 6 February 2020.
7. ^ "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. ^ "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.

External links

• 3D macromolecular structures of Coxsackieviruses from the EM Data Bank(EMDB)

• Enteroviruses
• Unaccepted virus taxa
• Polyphyletic groups