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Picornavirus Infections

Background

The Picornaviridae family (picornaviruses) causes a wider range of illnesses than most other, if not all, virus families. Infection with various picornaviruses may be asymptomatic or may cause clinical syndromes such as aseptic meningitis (the most common acute viral disease of the CNS), encephalitis, the common cold, febrile rash illnesses (hand-foot-and-mouth disease), conjunctivitis, herpangina, myositis and myocarditis, and hepatitis.

Poliomyelitis, caused by the enteroviral type species, was one of the first recorded infections; an Egyptian tomb carving showed a man with a foot-drop deformity typical of paralytic poliomyelitis.

Characteristics

The term Picornaviridae is derived from pico, which means small (typically, 18-30 nm), and RNA, referring to the single-stranded positive-sense RNA common to all members of the Picornaviridae family.
All members of this family, whose RNA molecules range from 7.2-8.5 kilobases (kb) in size, lack a lipid envelope and are therefore resistant to ether, chloroform, and alcohol. However, ionizing radiation, phenol, and formaldehyde readily inactivate picornaviruses.

The viral capsid of picornaviruses consists of a densely packed icosahedral arrangement of 60 protomers. Each protomer consists of 4 polypeptides, etoposide (VP) 1, 2, 3, and 4, which all derive from the cleavage of a larger protein. The capsid-coat protein serves multiple functions, including (1) protecting the viral RNA from degradation by environmental RNase, (2) determining host and tissue tropism by recognition of cell-specific cell-membrane receptors, (3) penetrating target cells and delivering the viral RNA into the cell cytoplasm, and (4) selecting and packaging viral RNA.

Two genera of Picornaviridae— enterovirus and rhinovirus —have an identical morphology but can be distinguished based on clinical, biophysical, and epidemiological studies. Enteroviruses grow at a wide pH range (ie, 3-10). After initial replication in the oropharynx, enteroviruses survive the acidic environment of the stomach. The small intestine is the major invasion site of enteroviruses, which replicate best at 37°C. Rhinoviruses replicate at a pH of 6-8. After initial replication in the nasal passages, the acidic environment of the stomach destroys rhinoviruses. Rhinoviruses optimally replicate at 33°C and primarily infect the nasal mucosa.

Classification

Overall, the family Picornaviridae includes 9 genera. In addition to the major human enteroviral pathogens (poliovirus, enterovirus, coxsackievirus, echovirus), rhinoviruses (approximately 105 serotypes), the human hepatitis A virus (HAV), and several parechoviruses, Picornaviridae contains several other genera of viruses that infect nonhuman vertebrate hosts.

Enteroviruses have several subgroups: 3 serotypes of polioviruses, 23 serotypes of group A coxsackieviruses, 6 serotypes of group B coxsackieviruses, and at least 31 serotypes of echoviruses. (ECHO virus is a misnomer based on the acronym enteric cytopathic human orphan virus.) Viruses are grouped according to pathogenicity, host range, and serotype, which is based on serum neutralization. Some enteroviruses are not classified further but rather assigned a number, currently 68 to 71. Bovine, equine, simian, porcine, and rodent enteroviruses also exist.

Cardiovirus (type species, encephalomyocarditis virus) is a classic infection in mice, although it has been observed to cause disease in humans.
Certain strains of this virus are associated with the development of diabetes in certain strains of mice and are used as a model for virus-associated insulin-requiring diabetes in humans.

Aphthovirus (type species, foot-and-mouth disease virus [FMDV]) creates a major worldwide economic problem, particularly in South America and Australia. FMDV, which has 7 serotypes, is largely controlled by the immunization or slaughter of infected animals. Aphthoviruses are more acid-labile than other picornaviruses.

The other genera include Parechovirus, Erbovirus (equine rhinitis B virus), Kobuvirus (Aichi virus), and Teschovirus (porcine teschovirus). Arthropod-infecting viruses, including Cricket paralysis virus, Drosophila C virus, and Tussock moth virus, are additional unclassified picornaviruses.

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