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. [1, 2]
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.
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. [5, 6]
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.
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.
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.
The pathogenesis of picornaviral infection is best understood for polioviruses, whose pathophysiology is similar to other picornaviruses except for tissue tropism after viremia. Of note, not all picornaviruses spread from the initial site of infection (eg, rhinoviruses). 
The replication cycle of picornaviruses is approximately 8 hours, with the exact duration depending on variables such as pH, temperature, cell type, and number of viral particles that infect the cell. The cycle proceeds in host cell cytoplasm, can occur in enucleated cells, and is not inhibited by actinomycin D. Although lytic infections are the rule, HAV can cause nonlytic infections that persist indefinitely. [9, 10]
Cellular protein synthesis declines precipitously after infection, possibly because of the interference with the 5' end of eukaryotic mRNA. A virus-encoded, RNA-dependent RNA polymerase, which produces negative-sense strands, copies the genomic RNA. These strands serve as templates for the positive-sense RNA synthesis. [9, 11]
In most picornaviral infections, infected cells growing in tissue culture show characteristic morphologic changes.  Within an hour of infection, margination of the chromatin occurs, in which normally homogeneous nuclear material begins to accumulate on the inside of the nuclear envelope. By 2.5-3 hours, membranous vesicles appear in the cytoplasm, beginning around the nuclear membrane and spreading outward. This vesiculation is associated with changes in the permeability of the cellular plasma membrane and eventual shriveling of the cell. Crystals of virus can be observed late in the process. The cytopathic effect appears mediated, at least in part, by a redistribution of lysosomal enzymes.
The antigenic structure of each viral capsid allows it to bind to specific cell membrane components. The virus uses these membrane receptors to enter the target cell. Different viruses use different identifiable receptors, and receptors may vary even among the same genus. For example, most human rhinoviruses bind to the intracellular adhesion molecule 1 (ICAM-1), an immunoglobulinlike molecule; others use a low-density lipoprotein receptor.  Families among the picornaviruses may use the same receptor, which may be shared by unrelated viruses.
Human enteroviral infections occur primarily via ingestion of fecally contaminated material (ie, fecal-oral route). The ingested virus replicates in susceptible tissues of the pharynx or gut. Enteroviral replication can be observed in lymphoid tissue of the small intestine within 24-72 hours of ingestion of the virus.
After multiplication in submucosal lymphatic tissues, enteroviruses pass to regional lymph nodes and give rise to a minor viremia that is transient and usually undetectable. During this low-grade viremia, the virus can spread to reticuloendothelial tissue (eg, liver, spleen, bone marrow, distant lymph nodes).
In subclinical infections, which are the most common, viral replication ceases after minor viremia because it is contained by host defense mechanisms. In a minority of infected individuals, however, further virus replication occurs in these reticuloendothelial sites, leading to major viremia. Major viremia can result in dissemination to target organs (eg, CNS, heart, skin), where necrosis and inflammatory lesions can occur. In target organs, the degree of inflammatory change and tissue necrosis corresponds to viral titer. Exercise, cold exposure, malnutrition, pregnancy, immunosuppression, and radiation can enhance the severity of the infection; enteroviral infection in persons with HIV infection may result in chronic enteroviral meningitis.
The overall incidence of picornavirus infections is unknown.
Most enteroviruses survive well in moist or wet environments and are readily transmitted via the fecal-oral route. Enteroviral infections occur not only in warmer climates, where they may be endemic year-round, but also with more seasonal periodicity in temperate climates (particularly during summer and fall months). 
Rhinoviruses have a well-established seasonal pattern that differs from those of enteroviral infections. In temperate climates, rhinoviral infections have fall and spring peaks; early-fall outbreaks of rhinoviral colds characteristically herald the respiratory disease season. In tropical areas, rhinovirus outbreaks occur during the rainy season; in the arctic, outbreaks occur during colder weather. 
Poliomyelitis eradication projects have typically involved mass vaccine administration with secondary emphasis on hygiene measures. By 1994, poliomyelitis was considered eradicated from the Americas. As of 2008, poliomyelitis was considered endemic in only 4 countries—Nigeria, India, Pakistan, and Afghanistan—accounting for 1392 of 1491 cases reported in 2008 (as of November 14, 2008). 
Picornaviruses cause various illnesses. Different viruses produce different clinical pictures; in addition, a given picornavirus type can cause varying manifestations in different hosts.
HAV infection may result in fatal fulminant hepatitis. Enteroviruses, particularly enterovirus 71, may cause fatal encephalitis. Infection with coxsackieviruses may lead to nonischemic cardiomyopathy, either chronic or fulminant in nature, and has been reported to cause fatal pneumonitis.  Parechoviruses have been observed to cause severe, even fatal, sepsis.  Poliomyelitis may be fatal if respiratory support is unavailable or ineffective.
Although many picornaviral infections are asymptomatic, short-term morbidity is the rule in those that do cause symptoms.  Gastrointestinal and upper respiratory tract symptoms are most common. Long-term morbidity is uncommon, except for persistent neurologic deficits as a consequence of meningoencephalitis, [17, 25] chronic nonischemic cardiomyopathy, or persistent paralysis (partial or complete) or postpolio syndrome.
Picornaviral infections have no known racial predilection.
The vast majority of enteroviral infections in children are asymptomatic. Some enteroviral infections, particularly those of the CNS, are more common in boys than in girls. After puberty, the reverse is true, perhaps because women have greater exposure to children who shed the virus and because of the relative immunosuppression of pregnancy.
Most picornavirus infections have no age predilection, although clinical manifestations may favor certain age groups. Aseptic meningitis is most common in very young infants, whereas myocarditis and pleurodynia are most prevalent in adolescents and young adults. 
Enteroviruses: The risk of certain enterovirus-related clinical syndromes varies with age and sex. Enteroviral infections occur predominantly in children. In enteroviral infections, antibody prevalence rates of a few serotypes indicate that, after the decline of passively acquired maternal antibodies (by age 6 mo), the fraction of immune persons in the population rises progressively with age; 15%-90% of the adult population has type-specific neutralizing antibodies. Symptomatic enteroviral infections are uncommon in elderly persons. Approximately 95% of infections caused by poliovirus and at least 50% of enteroviral infections that are not associated with polio are presumed completely asymptomatic. 
Rhinovirus: Prevalence studies of rhinovirus antibody show rapid acquisition of antibody during childhood and adolescence, with peak prevalence in young adults. Colds range from 1.2 infections per year in children younger than 1 year to 0.7 infections per year in young adults. Approximately 70%-88% of rhinovirus infections are associated with symptomatic respiratory illness.