| Coxsackie A virus | |
|---|---|
Virus classification  | |
| (unranked): | Virus |
| Realm: | Riboviria |
| Kingdom: | Orthornavirae |
| Phylum: | Pisuviricota |
| Class: | Pisoniviricetes |
| Order: | Picornavirales |
| Family: | Picornaviridae |
| Genus: | Enterovirus |
| Species: | |
| Strain: | Coxsackie A virus |
Coxsackie A virus (CAV) is a cytolytic Coxsackievirus of the Picornaviridae family, an enterovirus (a group containing the polioviruses, coxsackieviruses, and echoviruses).
Coxsackie A virus is a subgroup of enterovirus A, which are small, non-enveloped, positive-sense, single-stranded RNA viruses. Its protective, icosahedral capsid has an external portion that contains sixty copies of viral proteins (VP1,-2,-3) and an internal portion surrounding the RNA genome containing sixty copies of VP4 viral proteins. This capsid mediates cell entry and elicits the humoral immune responses. [2] Enteroviruses have a depression encircling each fivefold axis (canyon), which is their binding site for immunoglobulin-like receptors. This binding can trigger viral expansion and release of its genome. [3]
A complete genome analysis of Coxsackie virus A2, A4, A5, and A10 strains isolated from individuals with hand-foot-mouth disease showed that natural recombination is frequent in the virus's evolution. Its strains in China were related to strains in Mongolia, Taiwan, likely to those that circulated in Europe, and form a distinct lineage from strains imported from Japan and South Korea. [4]
Replication of the coxsackie virus happens through contributions of the host and virus components. The virus enters the cell where it is internalized into endoplasmic reticulum and the Golgi apparatus. After viral un-coating, viral RNA is released. Ribosomes on the rough endoplasmic reticulum translate the RNA into viral polyprotein. [5] This polyprotein is processed into structural protein P1 and non-structural proteins P2 and P3. Via the virus-encoded proteinase, P1 is processed into the viral capsid subunit proteins VP0, -1, -3. The 5'-non-coding region contains sequences that control genome replication and translation, while the 3'-non-coding region contains polyA tail needed for virus infectivity. [6]
The most well known Coxsackie A disease is hand, foot and mouth disease (unrelated to foot-and-mouth disease), a common childhood illness which affects mostly children aged 5 or under, [7] often produced by Coxsackie A16. In most individuals, infection is asymptomatic or causes only mild symptoms. In others, infection produces short-lived (7–10 days) fever and painful blisters in the mouth (a condition known as herpangina ), on the palms and fingers of the hand, or on the soles of the feet. There can also be blisters in the throat, or on or above the tonsils. Adults can also be affected. The rash, which can appear several days after high temperature and painful sore throat, can be itchy and painful, especially on the hands/fingers and bottom of feet. [8]
Other diseases include acute haemorrhagic conjunctivitis (A24 specifically), herpangina, and aseptic meningitis (both Coxsackie A and B viruses). Coxsackievirus A7 is associated with neurological diseases and can cause paralytic poliomyelitis. [9]
Coxsackie A virus leads to a number of diseases, however the most common signs and symptoms that appear with infection are fever and flu-like symptoms, mouth sores, and skin rashes. People who are infected may present with a mild fever and sore throat, and a general discomfort three to six days subsequent to exposure. Painful mouth sores (herpangina) may be present in the back of the mouth. These sores usually appear 24 hours after the flu like symptoms begin, and may blister, causing further discomfort when eating or drinking. A flat, red skin rash may appear, commonly accompanied by fluid filled blisters and scabbing. Rash will commonly present on the bottom of the feet, palm of hands, and other areas of the body, and persists upwards to ten days. [8] [10]
When the symptoms are incredibly severe, some may require hospitalization due to dehydration caused by inability to swallow food or water without pain, or seizures and convulsions can occur due to high fever. Signs of dehydration include dry skin, unintentional weight loss, or decreased urine output/darkened urine and if present should refer to a health care provider for intervention. Other serious complications include inflammatory brain conditions, such as viral meningitis or encephalitis, which require medical intervention. [11] A professional health care may need to monitor if the someone infected is immunocompromised, or the symptoms do not improve within ten days. [12] [8] [13]
The diagnosis of this disease centers around the appearance and behavior of fever, rash and mouth sores. Outside of the symptoms, age is also taken into consideration as the most common age of infection is under five years of age. [8] A healthcare professional may choose to confirm the diagnosis through collecting samples from mouth sores and skin blisters, or a stool sample may also be ordered to rule out any other causes. [12]
Since 2008, coxsackievirus A6 (CVA6) has been associated with several worldwide outbreaks of hand, foot and mouth disease (HFMD). [14] In Finland, the initial HFMD case caused by the CVA6 lead to its identification of being the responsible pathogen of the outbreaks in Europe, North America, and Asia. [15] Coxsackievirus A16 (CVA16) has also been linked to HFMD. [16]
Outbreaks are more commonly seen amongst children (those seven and younger) compared to outbreaks rates amongst adults. Due to this, there are outbreaks within daycares, summer camps, and early autumn. [17]
Serious pregnancy complications due to hand, foot, and mouth disease are rare due to its limited data. [18] However, HFMD is concerning if the mother contracts the virus at the end of her pregnancy. CVA16 infection has been associated with third trimester massive perivillous fibrin deposition leading to intrauterine death. [19] It has also led to first trimester spontaneous abortions. [16] Overall, there is limited information about the Coxsackievirus A strain in pregnant women.
On the other hand, there has been some reports of the Coxsackievirus B (CVB) with regards to pregnant women. Contraction of the CVB are not associated with a higher risk of spontaneous abortions. [20] Although, complications at the end of the pregnancy carries an increased risk of stillbirth or HFMD in the child. [20] There have been reports of congenital heart defects and urogenital anomalies within the newborns of women who seroconverted to CVB during pregnancy. [20] CVB is responsible for up to half of all individuals with pediatric myocarditis. [21] In the past, it has been stated that newborns who have contracted CVB have a 75% mortality from myocarditis. [22]
The Coxsackie A Virus is a highly contagious virus that commonly causes the mild hand, foot, and mouth disease but complications may lead to more serious diseases that can affect the heart, lungs, muscles, and more.[ citation needed ] The modes of transmission of the Coxsackie virus is primarily through contact between people, respiratory droplets (fluid from coughing and sneezing), and contaminated surfaces. [23] All age groups can become infected with the Coxsackie virus, however it occurs most frequently in young children under the age of 10 and in who have a weakened immune system. [23]
The main ways the Coxsackie Virus spreads are:
Although adults are less susceptible to infection, it is still possible for an adult to get infected with the Coxsackie virus. If a pregnant mother is infected, there is a 30-50% chance the infection will be passed on to the infant. [25]
There is no vaccine to reduce the chances of infection and spread. [26] It is critical to use non-pharmacological interventions to reduce the spread and transmission of Coxsackie virus. The best and most effective strategy for prevention is adopting proper hand hygiene, avoiding contact with the infected, abstain from touching mucous membranes of the face, and sanitizing frequently touched surfaces. [27]
Some of those who are infected with the Coxsackie virus may have complications that may lead to more serious issues. Complications include stomatitis, meningitis, pulmonary edema, myocarditis, pneumonia, and possibly spontaneous abortions. [23]
Treatment is dependent on the disease process initiated by the virus. There is no known cure or vaccine against this virus. [13]
Most Coxsackie A virus infections are mild and self-limiting meaning the infection has the ability to resolve on its own without requiring treatment. Symptoms of a Coxsackie A infection tend to dissipate on their own within 7–10 days. [13] [23] Treatment tends to focus on supportive care where the symptoms of the infection are targeted but not the virus itself. NSAIDs such as ibuprofen/naproxen and acetaminophen can be used to manage the flu-like symptoms, fever, and any other pain the infected individual may be feeling. [13] [23] Do not give a child aspirin as it may increase the risk of Reye syndrome. [28] Fluids are recommended as to decrease the chances of dehydration. Mouth sores will make eating and drinking painful and may potentially lead to loss of appetite and refusing to eat in order to prevent mouth and throat pain. [28] Severe dehydration may lead to hospitalization. Additionally, topical oral analgesic medications or salt water rinses can be used to help numb the sores and ease the throat pain. Since Coxsackie A is a viral infection, antibiotics will have no effect on the infection as they only work on bacterial infections. [13]
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.
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.
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.
Fifth disease, also known as erythema infectiosum and slapped cheek syndrome, is a common and contagious disease caused by infection with parvovirus B19. This virus was discovered in 1975 and can cause other diseases besides fifth disease. Fifth disease typically presents as a rash and is most common in children. While parvovirus B19 can affect people of all ages, only two out of ten individuals will present with symptoms.
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.
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.
Shingles, also known as herpes zoster or zona, is a viral disease characterized by a painful skin rash with blisters in a localized area. Typically the rash occurs in a single, wide mark either on the left or right side of the body or face. Two to four days before the rash occurs there may be tingling or local pain in the area. Other common symptoms are fever, headache, and tiredness. The rash usually heals within two to four weeks, but some people develop ongoing nerve pain which can last for months or years, a condition called postherpetic neuralgia (PHN). In those with poor immune function the rash may occur widely. If the rash involves the eye, vision loss may occur.
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.
Gingivostomatitis is a combination of gingivitis and stomatitis, or an inflammation of the oral mucosa and gingiva. Herpetic gingivostomatitis is often the initial presentation during the first ("primary") herpes simplex infection. It is of greater severity than herpes labialis which is often the subsequent presentations. Primary herpetic gingivostomatitis is the most common viral infection of the mouth.
Adenovirus infection is a contagious viral disease, caused by adenoviruses, commonly resulting in a respiratory tract infection. Typical symptoms range from those of a common cold, such as nasal congestion, coryza and cough, to difficulty breathing as in pneumonia. Other general symptoms include fever, fatigue, muscle aches, headache, abdominal pain and swollen neck glands. Onset is usually two to fourteen days after exposure to the virus. A mild eye infection may occur on its own, combined with a sore throat and fever, or as a more severe adenoviral keratoconjunctivitis with a painful red eye, intolerance to light and discharge. Very young children may just have an earache. Adenovirus infection can present as a gastroenteritis with vomiting, diarrhoea and abdominal pain, with or without respiratory symptoms. However, some people have no symptoms.
The schedule for childhood immunizations in the United States is published by the Centers for Disease Control and Prevention (CDC). The vaccination schedule is broken down by age: birth to six years of age, seven to eighteen, and adults nineteen and older. Childhood immunizations are key in preventing diseases with epidemic potential.
Herpes gladiatorum is one of the most infectious of herpes-caused diseases, and is transmissible by skin-to-skin contact. The disease was first described in the 1960s in the New England Journal of Medicine. It is caused by contagious infection with human herpes simplex virus type 1 (HSV-1), which more commonly causes oral herpes. Another strain, HSV-2 usually causes genital herpes, although the strains are very similar and either can cause herpes in any location.
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.
Chickenpox, also known as varicella, is a highly contagious, vaccine-preventable disease caused by the initial infection with varicella zoster virus (VZV), a member of the herpesvirus family. The disease results in a characteristic skin rash that forms small, itchy blisters, which eventually scab over. It usually starts on the chest, back, and face. It then spreads to the rest of the body. The rash and other symptoms, such as fever, tiredness, and headaches, usually last five to seven days. Complications may occasionally include pneumonia, inflammation of the brain, and bacterial skin infections. The disease is usually more severe in adults than in children.
A cold sore is a type of herpes infection caused by the herpes simplex virus that affects primarily the lip. Symptoms typically include a burning pain followed by small blisters or sores. The first attack may also be accompanied by fever, sore throat, and enlarged lymph nodes. The rash usually heals within ten days, but the virus remains dormant in the trigeminal ganglion. The virus may periodically reactivate to create another outbreak of sores in the mouth or lip.
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.
Coxsackieviruses-induced cardiomyopathy are positive-stranded RNA viruses in picornavirus family and the genus enterovirus, acute enterovirus infections such as Coxsackievirus B3 have been identified as the cause of virally induced acute myocarditis, resulting in dilated cardiomyopathy. Dilated cardiomyopathy in humans can be caused by multiple factors including hereditary defects in the cytoskeletal protein dystrophin in Duchenne muscular dystrophy (DMD) patients). A heart that undergoes dilated cardiomyopathy shows unique enlargement of ventricles, and thinning of the ventricular wall that may lead to heart failure. In addition to the genetic defects in dystrophin or other cytoskeletal proteins, a subset of dilated cardiomyopathy is linked to enteroviral infection in the heart, especially coxsackievirus B. Enterovirus infections are responsible for about 30% of the cases of acquired dilated cardiomyopathy in humans.
Picornain 3C is a protease found in picornaviruses, which cleaves peptide bonds of non-terminal sequences. Picornain 3C’s endopeptidase activity is primarily responsible for the catalytic process of selectively cleaving Gln-Gly bonds in the polyprotein of poliovirus and with substitution of Glu for Gln, and Ser or Thr for Gly in other picornaviruses. Picornain 3C are cysteine proteases related by amino acid sequence to trypsin-like serine proteases. Picornain 3C is encoded by enteroviruses, rhinoviruses, aphtoviruses and cardioviruses. These genera of picoviruses cause a wide range of infections in humans and mammals.
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.
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