Enteroviral 3′ UTR Element
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''Enterovirus'' is a genus of
positive-sense In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context, ...
single-stranded
RNA virus An RNA virus is a virus characterized by a ribonucleic acid (RNA) based genome. The genome can be single-stranded RNA (ssRNA) or double-stranded (Double-stranded RNA, dsRNA). Notable human diseases caused by RNA viruses include influenza, SARS, ...
es associated with several human and mammalian diseases. Enteroviruses are named by their transmission-route through the intestine ('enteric' meaning intestinal).
Serologic Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mi ...
studies have distinguished 71 human enterovirus
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 on the basis of
antibody An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...
neutralization tests. Additional
antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
ic variants have been defined within several of the serotypes on the basis of reduced or nonreciprocal cross-neutralization between variant strains. On the basis of their
pathogenesis In pathology, pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes . Descript ...
in humans and animals, the enteroviruses were originally classified into four groups,
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 ...
es,
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). Viral structure and genome Coxsackie A virus is a subgroup of ente ...
es (CA),
Coxsackie B virus Coxsackie B is a group of six serotypes of coxsackievirus (CVB1-CVB6), a pathogenic enterovirus, that trigger illnesses ranging from a mild febrile rash to full-fledged pericarditis and myocarditis ( coxsackievirus-induced cardiomyopathy). The ...
es (CB), and
echovirus Echovirus is a polyphyletic group of viruses associated with enteric disease in humans. The name is derived from "enteric cytopathic human orphan virus". These viruses were originally not associated with disease, but many have since been identifi ...
es, but it was quickly realized that there were significant overlaps in the biological properties of viruses in the different groups. Enteroviruses isolated more recently are named with a system of consecutive numbers: EV-D68, EV-B69, EV-D70, EV-A71, etc., where genotyping is based on the VP1 capsid region. Enteroviruses affect millions of people worldwide each year and are often found in the respiratory secretions (e.g., saliva, sputum, or nasal mucus) and stool of an infected person. Historically,
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 ...
was the most significant disease caused by an enterovirus, namely
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 ...
. There are 81 non-polio and 3 polio enteroviruses that can cause disease in humans. Of the 81 non-polio types, there are 22 Coxsackie A viruses, 6 Coxsackie B viruses, 28 echoviruses, and 25 other enteroviruses. Poliovirus, as well as coxsackie and echovirus, is spread through 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 ...
. Infection can result in a wide variety of symptoms, including those of: mild respiratory illness (the
common cold The common cold, or the cold, is a virus, viral infectious disease of the upper respiratory tract that primarily affects the Respiratory epithelium, respiratory mucosa of the human nose, nose, throat, Paranasal sinuses, sinuses, and larynx. ...
),
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 ...
, acute
hemorrhagic Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, va ...
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 ...
,
aseptic meningitis Aseptic meningitis is the inflammation of the meninges, a membrane covering the brain and spinal cord, in patients whose cerebral spinal fluid test result is negative with routine bacterial cultures. Aseptic meningitis is caused by viruses, mycob ...
,
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 ...
, severe
neonatal In common terminology, a baby is the very young offspring of adult human beings, while infant (from the Latin word ''infans'', meaning 'baby' or 'child') is a formal or specialised synonym. The terms may also be used to refer to Juvenile (orga ...
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
-like disease, acute
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 ...
, and the related
acute flaccid myelitis 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 ...
.


Virology

Enteroviruses are members of the
picornavirus Picornaviruses are a group of related Viral envelope, 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 virus, positi ...
family, a large and diverse group of small
RNA viruses ''Orthornavirae'' is a kingdom of viruses that have genomes made of ribonucleic acid (RNA), including genes which encode an RNA-dependent RNA polymerase (RdRp). The RdRp is used to transcribe the viral RNA genome into messenger RNA (mRNA) and t ...
characterized by a single positive-strand genomic RNA. All enteroviruses contain a
genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
of approximately 7,500 bases and are known to have a high
mutation rate In genetics, the mutation rate is the frequency of new mutations in a single gene, nucleotide sequence, or organism over time. Mutation rates are not constant and are not limited to a single type of mutation; there are many different types of mu ...
due to low-fidelity replication and frequent recombination. After infection of the host cell, the genome is translated in a cap-independent manner into a single
polyprotein Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Protein degradation is a major regulatory mechanism of gene expression and contributes substantially to shaping mammalian proteomes. Uncatalysed, the hydrolysis o ...
, which is subsequently processed by virus-encoded
protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalysis, catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products ...
s into the structural
capsid 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 m ...
proteins and the nonstructural proteins, which are mainly involved in the replication of the virus.
RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
recombination appears to be a major driving force in the evolution of enteroviruses as well as in the shaping of their genetic architecture. The mechanism of recombination of the RNA
genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
likely involves template strand switching during
RNA replication 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 ...
, a process known as copy choice recombination. RNA recombination is considered to be an adaptation for dealing with RNA genome damage and a source of
genetic diversity Genetic diversity is the total number of genetic characteristics in the genetic makeup of a species. It ranges widely, from the number of species to differences within species, and can be correlated to the span of survival for a species. It is d ...
. It is also a source of concern for vaccination strategies, because live attenuated/mutated strains used for vaccination could potentially recombine with wild-type related strains, as has been the case with circulating vaccine derived polio viruses (cVDPDs). The capsid region and especially VP1 is a recombination coldspot, and this is one of the main reasons to use this region for genotyping. However, the 5'UTR - capsid junction and the beginning of the P2 region have been observed to recombine very frequently, although recombinations do occur in the rest of the genome as well. Interestingly, the enterovirus species EV-A, EV-B, EV-C, EV-D have not been observed so far to exchange genomic regions among them, with the exception of the 5'UTR.


Member viruses


Enterovirus A–L

Enteroviruses are a group of ubiquitous viruses that cause a number of infections which are usually mild. The genus enterovirus includes enteroviruses and rhinoviruses. Enterovirus A include coxsackievirus A2, A3, A4, A5, A6, A7, A8, A10, A12, A14, A16 and enterovirus A71, A76, A89, A90, A91, A92, A144, A119, A120, A121, A122 (simian virus 19), A123 (simian virus 43), A124 (simian virus 46), A125 (baboon enterovirus A13). Some viruses initially reported as novel have been found to be misidentified. Thus, coxsackievirus A23 is the same serotype as echovirus 9, and coxsackievirus A15 is the same serotype as coxsackievirus A11 and coxsackievirus A18 is the same serotype as coxsackievirus A13. Coxsackie A16 virus causes human
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 ...
. Enterovirus B includes coxsackievirus B1,2,3,4,5,6; coxsackievirus A9; echovirus 1–33 and enterovirus B69–113. Coxsackie B viruses are found worldwide and can cause
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 ...
(inflammation of the heart);
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 ...
(inflammation of the sac surrounding the heart);
meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasion ...
(inflammation of the membranes that line the brain and spinal cord); and
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 ...
(inflammation of the pancreas). The Coxsackie B viruses are also reported to cause a spastic paralysis due to the degeneration of neuronal tissue and muscle injury. Infections usually occur during warm summer months with symptoms including exanthema, pleurodynia, flu-like illness consisting of fever, fatigue, malaise, myalgia, nausea, abdominal pain and vomiting.
Echovirus Echovirus is a polyphyletic group of viruses associated with enteric disease in humans. The name is derived from "enteric cytopathic human orphan virus". These viruses were originally not associated with disease, but many have since been identifi ...
es are a cause of many of the nonspecific viral infections that can range from minor illness to severe, potentially fatal conditions such as aseptic meningitis, encephalitis, paralysis and myocarditis. It is mainly found in the intestine, and can cause nervous disorders. Type B enteroviruses are responsible for a vast number of mild and acute infections. They have been reported to remain in the body causing persistent infections contributing to chronic diseases such as type I diabetes. Enterovirus C consists of polioviruses 1,2 and 3; coxsackieviruses A1, A11, A13, A18, A17, 20, A21, A22, A24 and enterovirus C95, C96, C99, C102, C104, C105, C109, C113, C118. The three serotypes of poliovirus, PV-1, PV-2, and PV-3 each have a slightly different capsid protein. Capsid proteins define cellular receptor specificity and virus antigenicity. PV-1 is the most common type to cause infection in humans; however, all three forms are extremely contagious spreading through person-to-person contact. Poliovirus causes Polio, or Poliomyelitis, which is a disabling and life-threatening disease that causes paresthesia, meningitis and permanent paralysis. Symptoms can include sore throat, fever, tiredness, nausea, headache and stomach pain although 72% of those that get infected will not display visible symptoms. There are two types of vaccines available to prevent polio: inactivated poliovirus vaccine given as an injection in the leg (IPV) or arm and oral poliovirus vaccine (OPV). The polio vaccine is highly efficacious giving protection to 99 out of 100 children vaccinated.


Persistent non-cytolytic enterovirus

Enteroviruses are capable of producing acute infections that are rapidly cleared by the adaptive immune response. However, genomic mutations which enterovirus B serotypes (such as coxsackievirus B and
echovirus Echovirus is a polyphyletic group of viruses associated with enteric disease in humans. The name is derived from "enteric cytopathic human orphan virus". These viruses were originally not associated with disease, but many have since been identifi ...
) may acquire in the host during the acute phase of the infection can transform these viruses into the non-cytolytic form (also known as non-cytopathic or defective enterovirus), a form which is capable of causing persistent low-level infections in human tissues that can last indefinitely. This persistent non-cytolytic enterovirus is a mutated
quasispecies The quasispecies model is a description of the process of the Darwinian evolution of certain self-replicating entities within the framework of physical chemistry. A quasispecies is a large group or "cloud" of related genotypes that exist in an env ...
, and such non-cytolytic infections have been found in the pancreas in
type 1 diabetes Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that occurs when the body's immune system destroys pancreatic cells (beta cells). In healthy persons, beta cells produce insulin. Insulin is a hormone require ...
, in chronic
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 ...
and
dilated cardiomyopathy Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. C ...
, in
valvular heart disease Valvular heart disease is any cardiovascular disease process involving one or more of the four valves of the heart (the aortic and mitral valves on the left side of heart and the pulmonic and tricuspid valves on the right side of heart). The ...
, in the muscles, intestines and brain in
myalgic encephalomyelitis Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling chronic illness. People with ME/CFS experience profound fatigue that does not go away with rest, as well as sleep issues and problems with memory or concentration. T ...
, and in Sjögren's syndrome. In these persistent infections, enteroviral RNA is present at low levels in the tissues (both as single-stranded viral RNA, and in the more immune resistant doubled-stranded RNA form). Some researchers believe this enteroviral RNA is just a remnant of the acute infection, although other scientists believe these persistent intracellular viral RNA infections may have pathological effects, playing a causal role their associated diseases.


Enterovirus D68

EV-D68 first was identified in California in 1962. Compared with other enteroviruses, it has been rarely reported in the U.S. in the past 40 years. Most people who get infected are infants, children, and teens. EV-D68 usually causes mild to severe respiratory illness; however, the full spectrum of EV-D68 illness is not well-defined. Most start with common cold symptoms of runny nose and cough. Some, but not all, may also have fever. For more severe cases, difficulty breathing, wheezing or problems catching your breath may occur. As of October 4, 2014, there has been one death in New Jersey directly linked to EV-D68, as well as one death in Rhode Island attributed to a combination of EV-D68 and sepsis caused by an infection of ''
Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...
''.


Enterovirus A71

Enterovirus A71 (EV-A71) is notable as one of the major causative agents for
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 ...
(HFMD), and is sometimes associated with severe central nervous system diseases. EV-A71 was first isolated and characterized from cases of neurological disease in California in 1969. To date, little is known about the molecular mechanisms of host response to EV-A71 infection, but increases in the level of mRNAs encoding chemokines, proteins involved in protein degradation, complement proteins, and proapoptotis proteins have been implicated.


Poliovirus

There are three
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 of poliovirus, ''PV-1'', ''PV-2'', and ''PV-3''; each with a slightly different
capsid 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 m ...
protein. Capsid proteins define cellular receptor specificity and virus antigenicity. ''PV-1'' is the most common form encountered in nature; however, all three forms are extremely
infectious infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
. Poliovirus can affect the
spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...
and cause
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 ...
. ''Polioviruses'' were formerly classified as a species belonging to the genus Enterovirus in the family Picornaviridae. The Poliovirus species has been eliminated from the genus Enterovirus. The following serotypes, Human poliovirus 1, Human poliovirus 2, and Human poliovirus 3, were assigned to the species Human enterovirus C, in the genus Enterovirus in the family Picornaviridae. The type species of the genus Enterovirus was changed from Poliovirus to Human enterovirus C. This has been ratified in April 2008. The 39th Executive Committee (EC39) of the International Committee on Taxonomy of Viruses (ICTV) met in Canada during June 2007 with new taxonomic proposals. Two of the proposals with three changes were: * Code 2005.261V.04: To remove the following species Poliovirus from the existing genus Enterovirus in the family Picornaviridae. * Code 2005.262V.04: To assign the viruses; PV-1, PV-2, PV-3 to the existing species Human enterovirus C in the genus Enterovirus in the family Picornaviridae. * Code 2005.263V.04: To change the type species Poliovirus from the existing genus Enterovirus in the family Picornaviridae to the type species Human enterovirus C. Proposals approved at the (EC39) meeting of 2007, were sent to members of ICTV via email for ratification and have become official taxonomy. There have been a total of 215 taxonomic proposals, which have been approved and ratified since the 8th ICTV Report of 2005. The ratification process was performed by email. The proposals were sent electronically via email on March 18, 2008, to ICTV members with a request to vote on whether to ratify the taxonomic proposals, with a 1-month deadline. The following are two of the taxonomic proposals with three changes that were ratified by ICTV members in April 2008: Picornaviruses * 2005.261V.04: To remove the following species from the existing genus Enterovirus in the family Picornaviridae: Poliovirus. (Note: Poliovirus hereby loses its status as a virus species.) * 2005.262V.04: To assign the following viruses to the species Human enterovirus C in the existing genus Enterovirus in the family Picornaviridae: Human poliovirus 1, Human poliovirus 2, Human poliovirus 3. (This is not strictly necessary as a taxonomic proposal because it concerns entities below the species level, but it is left in to clarify this reorganization of the Picornaviridae.) * 2005.263V.04: To change the type species of the genus Enterovirus in the family Picornaviridae, from Poliovirus to Human enterovirus C.


Diseases caused by enterovirus infection

Enteroviruses cause a wide range of symptoms, and while their long list of signs and symptoms should put them on the differential diagnosis list of many illnesses, they often go unnoticed. Enteroviruses can cause anything from rashes in small children, to summer colds, to encephalitis, to blurred vision, to
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 ...
. Enteroviral infections have a great range in presentation and seriousness. Non polio enteroviruses cause 10–15 million infections and tens of thousands of hospitalizations in the US each year. Enteroviruses can be identified through cell culture or PCR assay, collected from fecal or respiratory specimens. Below are common enterovirus related diseases, including poliomyelitis. *
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 ...
primarily via the fecal-oral route *
Polio-like syndrome Polio-like syndrome is a general description of a group of symptoms which mimic polio, including rarely permanent paralysis. Various triggers have been found, including some viruses from the same virus group as polio: enterovirus 68, enterovirus 7 ...
found in children who tested positive for
enterovirus 68 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 ...
. * Nonspecific
febrile Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with body temperature exceeding the normal range caused by an increase in the body's temperature set point in the hypothalamus. There is no single agre ...
illness is the most common presentation of enterovirus infection. Other than fever, symptoms include muscle pain, sore throat, gastrointestinal distress/abdominal discomfort, and headache. In newborns the picture may be that of
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
, however, and can be severe and life-threatening. * Enteroviruses are by far the most common causes of
aseptic meningitis Aseptic meningitis is the inflammation of the meninges, a membrane covering the brain and spinal cord, in patients whose cerebral spinal fluid test result is negative with routine bacterial cultures. Aseptic meningitis is caused by viruses, mycob ...
in children. In the United States, enteroviruses are responsible for 30,000 to 50,000 meningitis hospitalizations per year as a result of 10–15 million infections. *
Bornholm disease 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 tha ...
or epidemic pleurodynia is characterized by severe paroxysmal pain in the chest and abdomen, along with fever, and sometimes nausea, headache, and
emesis Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pregna ...
. *
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/or
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 ...
are typically caused by enteroviruses; symptoms consist of fever with
dyspnea Shortness of breath (SOB), known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing discomfort that ...
and
chest pain Chest pain is pain or discomfort in the chest, typically the front of the chest. It may be described as sharp, dull, pressure, heaviness or squeezing. Associated symptoms may include pain in the shoulder, arm, upper abdomen, or jaw, along with n ...
.
Arrhythmias Arrhythmias, also known as cardiac arrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – above 100 beats ...
, heart failure, and myocardial infarction have also been reported. *
Acute hemorrhagic conjunctivitis Acute hemorrhagic conjunctivitis (AHC) (also spelled acute haemorrhagic conjunctivitis) is a derivative of the highly contagious conjunctivitis virus, otherwise known as pink eye. Symptoms include excessively red, swollen eyes as well as subconj ...
can be caused by enteroviruses. *
Herpangina Herpangina, also called mouth blisters, is a painful mouth infection caused by coxsackieviruses. Usually, herpangina is produced by one particular strain of coxsackie virus A (and the term "herpangina virus" refers to coxsackievirus A), but it can ...
is caused by Coxsackie A virus, and causes a vesicular rash in the oral cavity and on the
pharynx The pharynx (: pharynges) is the part of the throat behind the human mouth, mouth and nasal cavity, and above the esophagus and trachea (the tubes going down to the stomach and the lungs respectively). It is found in vertebrates and invertebrates ...
, along with high fever,
sore throat Sore throat, also known as throat pain, is pain or irritation of the throat. The majority of sore throats are caused by a virus, for which antibiotics are not helpful. For sore throat caused by bacteria (GAS), treatment with antibiotics may hel ...
,
malaise In medicine, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. It is considered a vague termdescribing the state of simply not feeling well. The word has exist ...
, and often
dysphagia Dysphagia is difficulty in swallowing. Although classified under " symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right. It may be a sensation that suggests difficulty in the passage of solids or l ...
, loss of appetite, back pain, and headache. It is also self-limiting, with symptoms typically ending in 3–4 days. *
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 ...
is a childhood illness most commonly caused by infection by Coxsackie A virus or EV71. *
Encephalitis Encephalitis is inflammation of the Human brain, brain. The severity can be variable with symptoms including reduction or alteration in consciousness, aphasia, headache, fever, confusion, a stiff neck, and vomiting. Complications may include se ...
is rare manifestation of enterovirus infection; when it occurs, the most frequent enterovirus found to be causing it is
echovirus 9 Echovirus is a polyphyletic group of viruses associated with enteric disease in humans. The name is derived from "enteric cytopathic human orphan virus". These viruses were originally not associated with disease, but many have since been identifi ...
. *
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 ...
is characterized by inflammation of the myocardium (cardiac muscle cells). Over the last couple of decades, numerous culprits have been identified as playing a role in myocarditis pathogenesis in addition to the enterovirus, which at first was the most commonly implicated virus in this pathology. One of the most common enteroviruses found to be responsible for causing Myocarditis is the Coxsackie B3 virus. * A 2007 study suggested that acute respiratory or gastrointestinal infections associated with enterovirus may be a factor in
myalgic encephalomyelitis Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling chronic illness. People with ME/CFS experience profound fatigue that does not go away with rest, as well as sleep issues and problems with memory or concentration. T ...
.


Suspected diseases

Encephalitis lethargica Encephalitis lethargica (EL) is an atypical form of encephalitis. Also known as "von Economo Encephalitis", "sleeping sickness" or "sleepy sickness" (distinct from tsetse fly–transmitted sleeping sickness), it was first described in 1917 by ne ...
, the 1917–1926 "sleeping sickness".


Possible correlations being studied

Enterovirus has been speculated to be connected with
Type 1 diabetes Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that occurs when the body's immune system destroys pancreatic cells (beta cells). In healthy persons, beta cells produce insulin. Insulin is a hormone require ...
. It has been proposed that type 1 diabetes is a virus-triggered autoimmune response in which the immune system attacks virus-infected cells along with the insulin-producing beta cells in the pancreas. A team working at University of Tampere, Finland identified the enterovirus Coxsackievirus B1 as possibly linked to type 1 diabetes (which is an autoimmune disease). Enteroviruses, including polioviruses, may be a cause of
myalgic encephalomyelitis Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling chronic illness. People with ME/CFS experience profound fatigue that does not go away with rest, as well as sleep issues and problems with memory or concentration. T ...
/
chronic fatigue syndrome Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling Chronic condition, chronic illness. People with ME/CFS experience profound fatigue that does not go away with rest, as well as sleep issues and problems with memory ...
(ME/CFS).


Symptoms

Most people who contract enterovirus have mild symptoms lasting about a week. Those with higher risk may have more complications, sometimes becoming fatal. The most common sign of enterovirus is a
common cold The common cold, or the cold, is a virus, viral infectious disease of the upper respiratory tract that primarily affects the Respiratory epithelium, respiratory mucosa of the human nose, nose, throat, Paranasal sinuses, sinuses, and larynx. ...
. More intense symptoms of enterovirus include hypoxia,
aseptic meningitis Aseptic meningitis is the inflammation of the meninges, a membrane covering the brain and spinal cord, in patients whose cerebral spinal fluid test result is negative with routine bacterial cultures. Aseptic meningitis is caused by viruses, mycob ...
,
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 ...
,
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 ...
, and
paralysis Paralysis (: paralyses; also known as plegia) is a loss of Motor skill, motor function in one or more Skeletal muscle, muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory d ...
.


Treatment

Treatment for enteroviral infection is mainly supportive. In cases of pleurodynia, treatment consists of
analgesics An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...
to relieve the severe pain that occurs in patients with the disease; in some severe cases, opiates may be needed. Treatment for aseptic meningitis caused by enteroviruses is also mainly symptomatic. In patients with enteroviral carditis, treatment consists of the prevention and treatment of complications such as
arrhythmias Arrhythmias, also known as cardiac arrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – above 100 beats ...
,
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 ...
, and
cardiac failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF typically pre ...
. Other treatments that have been investigated for enteroviral carditis include
intravenous immunoglobulin Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin) to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory demyelinat ...
.


Taxonomy

The enterovirus
genus Genus (; : genera ) is a taxonomic rank above species and below family (taxonomy), family as used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In bino ...
includes the following fifteen species: * '' Enterovirus A'' (formerly ''Human enterovirus A'') * ''
Enterovirus B ''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 st ...
'' (formerly ''Human enterovirus B'') * ''
Enterovirus C 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-C ...
'' (formerly ''Human enterovirus C'') * ''
Enterovirus D Enterovirus D is a species of enterovirus which causes disease in humans. Five subtypes have been identified to date: *Enterovirus 68: causes respiratory disease, and is associated with acute flaccid paralysis (AFP) – a disease similar to poli ...
'' (formerly ''Human enterovirus D'') * ''
Enterovirus E ''Enterovirus E'' (formerly bovine enterovirus (BEV)) is a picornavirus of the genus ''Enterovirus''. The virus may also be referred to as enteric cytopathic bovine orphan virus (ECBO). It is endemic in cattle populations worldwide, and although ...
'' (formerly ''Bovine enterovirus'' group A) * '' Enterovirus F'' (formerly ''Bovine enterovirus'' group B) * '' Enterovirus G'' (formerly ''Porcine enterovirus B'') * '' Enterovirus H'' (formerly ''Simian enterovirus A'') * '' Enterovirus I'' * ''
Enterovirus J ''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 st ...
'' * '' Enterovirus K'' * '' Enterovirus L'' * ''
Rhinovirus A The rhinovirus (from the "nose", , romanized: "of the nose", and the ) is a positive-sense, single-stranded RNA virus belonging to the genus ''Enterovirus'' in the family ''Picornaviridae''. Rhinovirus is the most common viral infectious age ...
'' (formerly ''Human rhinovirus A'') * '' Rhinovirus B'' (formerly ''Human rhinovirus B'') * '' Rhinovirus C'' (formerly ''Human rhinovirus C'') These fifteen species'
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 ...
include: * Coxsackievirus ** ''Enterovirus A:'' serotypes CVA-2, CVA-3, CVA-4, CVA-5, CVA-6, CVA-7, CVA-8, CVA-10, CVA-12, CVA-14, and CVA-16. ** ''Enterovirus B:'' serotypes CVB-1, CVB-2, CVB-3, CVB-4, CVB-5, CVB-6, and CVA-9. ** ''Enterovirus C:'' serotypes CVA-1, CVA-11, CVA-13, CVA-17, CVA-19, CVA-20, CVA-21, CVA-22, and CVA-24. * Echovirus ** ''Enterovirus B:'' serotypes E-1, E-2, E-3, E-4, E-5, E-6, E-7, E-9, E-11 through E-21, E-24, E-25, E-26, E-27, E-29, E-30, E-31, E32, and E-33. * Enterovirus ** ''Enterovirus A:'' serotypes EV-A71, EV-A76, EV-A89 through EV-A92, EV-A114, EV-A119, EV-A120, EV-A121, SV19, SV43, SV46, and BabEV-A13. ** ''Enterovirus B:'' serotypes EV-B69, EV-B73 through EV-B75, EV-B77 through EV-B88, EV-B93, EV-B97, EV-B98, EV-B100, EV-B101, EV-B106, EV-B107, EV-B110 through EV-B113, and SA5. ** ''Enterovirus C:'' serotypes EV-C95, EV-C96, EV-C99, EV-C102, EV-C104, EV-C105, EV-C109, EV-C113, EV-C116, EV-C117, and EV-C118. ** ''Enterovirus D:'' serotypes EV-D68, EV-D70, EV-D94, EV-D111, and EV-D120. ** ''Enterovirus E:'' serotypes EV-E1, EV-E2, EV-E3, EV-E4, and EV-E5. ** ''Enterovirus F:'' serotypes EV-F1, EV-F2, EV-F3, EV-F4, EV-F5, EV-F6, and EV-F7. ** ''Enterovirus G:'' serotypes EV-G1 through EV-G20. ** ''Enterovirus H:'' serotype EV-H. ** ''Enterovirus I:'' serotype EV-I1 and EV-I2. ** ''Enterovirus J:'' serotypes: EV-J1, EV-J103, and EV-J108. ** ''Enterovirus K:'' serotype EV-K1 and EV-K2. ** ''Enterovirus L:'' serotype EV-L1. * Rhinovirus ** ''Rhinovirus A:'' serotypes RV-A1, RV-A1B, RV-A2, RV-A7 through RV-A13, RV-A15, RV-A16, RV-A18 through RV-A25, RV-A28 through RV-A34, RV-A36, RV-A38 through RV-A41, RV-A43, RV-A45 through RV-A47, RV-A49 through RV-A51, RV-A53 through RV-A68, RV-A71, RV-A73 through RV-A78, RV-A80 through RV-A82, RV-A85, RV-A88 through RV-A90, RV-A94, RV-A96, and RV-A100 through RV-A108 ** ''Rhinovirus B:'' serotypes RV-B3 through RV-B6, RV-B14, RV-B17, RV-B26, RV-B27, RV-B35, RV-B37, RV-B42, RV-B48, RV-B52, RV-B69, RV-B70, RV-B72, RV-B79, RV-B83, RV-B84, RV-B86, RV-B91 through RV-B93, RV-B97, and RV-B99 through RV-B104 ** ''Rhinovirus C:'' serotypes RV-C1 through RV-C51, RV-C54, RV-C55, and RV-C56. * Poliovirus ** ''Enterovirus C:'' serotypes PV-1, PV-2, and PV-3.


See also

*
Coxsackievirus Coxsackieviruses are a few related enteroviruses that belong to the ''Picornaviridae'' family of viral envelope, nonenveloped, linear, positive-sense single-stranded RNA viruses, as well as its genus ''Enterovirus'', which also includes poliovi ...
*
Echovirus Echovirus is a polyphyletic group of viruses associated with enteric disease in humans. The name is derived from "enteric cytopathic human orphan virus". These viruses were originally not associated with disease, but many have since been identifi ...
*
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 ...
*
Influenza Influenza, commonly known as the flu, is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These sympto ...
*
Influenza-like illness Influenza-like illness (ILI), also known as flu-like syndrome or flu-like symptoms, is a medical diagnosis of possible influenza or other illness causing a set of common symptoms. These include fever, shivering, chills, malaise, dry cough, loss ...


References


External links


ICTV International Committee on Taxonomy of Viruses (official site)


* ttp://www.alertnet.org/thenews/newsdesk/PEK295543.htm alertnet.org, FACTBOX-Q&A on hand, foot and mouth disease* {{Authority control Virus genera