Enterovirus


Enterovirus is a genus of positive-sense single-stranded RNA viruses associated with several human and mammalian diseases. Enteroviruses are named by their transmission-route through the intestine.
Serologic studies have distinguished 71 human enterovirus serotypes on the basis of antibody neutralization tests. Additional antigenic 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 humans and animals, the enteroviruses were originally classified into four groups, polioviruses, Coxsackie A viruses, Coxsackie B viruses, and echoviruses, 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.
Enteroviruses affect millions of people worldwide each year and are often found in the respiratory secretions and stool of an infected person. Historically, poliomyelitis was the most significant disease caused by an enterovirus, namely poliovirus. 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. Infection can result in a wide variety of symptoms, including those of: mild respiratory illness, hand, foot and mouth disease, acute hemorrhagic conjunctivitis, aseptic meningitis, myocarditis, severe neonatal sepsis-like disease, acute flaccid paralysis, and the related acute flaccid myelitis.

Virology

Enteroviruses are members of the picornavirus family, a large and diverse group of small RNA viruses characterized by a single positive-strand genomic RNA. All enteroviruses contain a genome of approximately 7,500 bases and are known to have a high mutation rate 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, which is subsequently processed by virus-encoded proteases into the structural capsid proteins and the nonstructural proteins, which are mainly involved in the replication of the virus.
RNA 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 likely involves template strand switching during RNA replication, 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.

Member viruses

Coxsackie and echovirus

es are a non-phylogenetic group. Coxsackie A viruses are mainly associated with human hand, foot and mouth disease. Coxsackie B viruses can cause signs and symptoms, similar to a cold, but these viruses also can lead to more serious diseases, including myocarditis ; pericarditis ; meningitis ; and pancreatitis.
Echoviruses are a cause of many of the nonspecific viral infections. It is mainly found in the intestine, and can cause nervous disorders. The usual symptoms of Coxsackie and echovirus are fever, mild rash, and mild upper respiratory tract illness.

Non-cytolytic (non-cytopathic) enterovirus

Enteroviruses are usually only capable of producing acute infections that are rapidly cleared by the adaptive immune response. However genome mutations, which enterovirus B serotypes may acquire in the host during the acute phase, may transform these viruses into the non-cytolytic form. This is a mutated quasispecies of enterovirus, which can cause persistent infection in human cardiac tissues especially in some patients with myocarditis or dilated cardiomyopathy. In persistent infections viral RNA is present only on very low levels and is not believed to contribute to any ongoing myocardial disease being a fading remnant of a recent acute infection although some scientists think otherwise.

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.

Enterovirus A71

Enterovirus A71 is notable as one of the major causative agents for hand, foot and mouth disease, 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 serotypes of poliovirus, PV-1, PV-2, and PV-3; each with a slightly different capsid 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. Poliovirus can affect the spinal cord and cause poliomyelitis.
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 of the International Committee on Taxonomy of Viruses met in Canada during June 2007 with new taxonomic proposals.
Two of the proposals with three changes were:
Proposals approved at the 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
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. 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.
, the 1917 - 1926 "sleeping sickness".

Treatment

Treatment for enteroviral infection is mainly supportive. In cases of pleurodynia, treatment consists of analgesics 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, pericardial effusion, and cardiac failure. Other treatments that have been investigated for enteroviral carditis include intravenous immunoglobulin.

Taxonomy

The enterovirus genus includes the following fifteen species:
These fifteen species' serotype include: