Enteroviruses are a genus of picornaviruses that mainly replicate in the gut. There are at least 71 serotypes divided into 5 groups: polioviruses, coxsackie A viruses, coxsackie B viruses, echoviruses, and newly identified enteroviruses. Enterovirus infections can range from subclinical to abortive infections with minor illness to major illness with paralysis. Prevention is focused on vaccination with oral or intramuscular poliovirus vaccines. While poliovirus has been largely eradicated, surveillance continues to monitor outbreaks and achieve global eradication.

1. Enteroviruses
AMIR RAJAEY

2. Enteroviruses
Enteroviruses are a genus of the picornavirus family which replicate
mainly in the gut.
Single stranded naked RNA virus with icosahedral symmetry
Unlike rhinoviruses, they are stable in acid pH
Capsid has 60 copies each of 4 proteins, VP1, VP2, VP3 and VP4
arranged with icosahedral symmetry around a positive sense genome.
At least 71 serotypes are known: divided into 5 groups
◦ Polioviruses
◦ Coxsackie A viruses
◦ Coxsackie B viruses
◦ Echoviruses
◦ Enteroviruses (more recently, new enteroviruses subtype have been allocated
sequential numbers (68-71))

3. Enterovirus Particles

4. Properties of Enteroviruses

5. Poliovirus
3 serotypes of poliovirus (1, 2, and3) but no common antigen.
Have identical physical properties but only share 36-52% nucleotide
homology.
Humans are the only susceptible hosts.
Polioviruses are distributed globally. Before the availability of
immunization, almost 100% of the population in developing countries
before the age of 5.
The availability of immunization and the poliovirus eradication campaign
has eradicated poliovirus in most regions of the world except in the Indian
Subcontinent and Africa.

6. Pathogenesis
The incubation period is usually 7 - 14 days.
Following ingestion, the virus multiplies in
the oropharyngeal and intestinal mucosa.
The lymphatic system, in particular the
tonsils and the Peyer's patches of the ileum
are invaded and the virus enters the blood
resulting in a transient viraemia.
In a minority of cases,the virus may involve
the CNS following dissemination.

8. pathogenicity

9. Clinical Manifestations
There are 3 possible outcomes of infection:
◦ Subclinical infection (90 - 95%) - inapparent subclinical infection account
for the vast majority of poliovirus infections.
◦ Abortive infection (4 - 8%) - a minor influenza-like illness occurs, recovery
occurs within a few days and the diagnosis can only be made by the
laboratory. The minor illness may be accompanied by aseptic meningitis
◦ Major illness (1 - 2%) - the major illness may present 2 - 3 days following
the minor illness or without any preceding minor illness. Signs of aseptic
meningitis are common. Involvement of the anterior horn cells lead to
flaccid paralysis. Involvement of the medulla may lead to respiratory
paralysis and death.

10. Laboratory Diagnosis
Virus Isolation
◦ Mainstay of diagnosis of poliovirus infection
◦ poliovirus can be readily isolated from throat swabs, faeces, and rectal
swabs. It is rarely isolated from the CSF
◦ Can be readily grown and identified in cell culture
◦ Requires molecular techniques to differentiate between the wild type
and the vaccine type.
Serology
◦ Very rarely used for diagnosis since cell culture is efficient.
Occasionally used for immune status screening for
immunocompromised individuals.

11. Prevention (1)
No specific antiviral therapy is available. However the disease may be
prevented through vaccination. There are two vaccines available.
Intramuscular Poliovirus Vaccine (IPV)
◦ consists of formalin inactivated virus of all 3 poliovirus serotypes.
◦ Produces serum antibodies only: does not induce local immunity and thus will not
prevent local infection of the gut.
◦ However, it will prevent paralytic poliomyelitis since viraemia is essential for the
pathogenesis of the disease.
Oral Poliovirus Vaccine (OPV)
◦ Consists of live attenuated virus of all 3 serotypes.
◦ Produces local immunity through the induction of an IgA response as well as
systemic immunity.
◦ Rarely causes paralytic poliomyelitis, around 1 in 3 million doses.

12. Prevention (2)
Most countries use OPV because of its ability to induce local immunity and also it
is much cheaper to produce than IPV.
The normal response rate to OPV is close to 100%.
OPV is used for the WHO poliovirus eradication campaign.
Because of the slight risk of paralytic poliomyelitis, some Scandinavian countries
have reverted to using IPV. Because of the lack of local immunity, small
community outbreaks of poliovirus infections have been reported.
Poliovirus was targeted for eradication by the WHO by the end of year 2000 (now
2005). To this end, an extensive monitoring network had been set up.
Poliovirus has been eradicated from most regions of the world except the Indian
subcontinent and sub-Saharan Africa. It is possible that the WHO target may be
achieved.

13. Current Status of Wild Poliovirus Transmission

14. Coxsackieviruses
Coxsackieviruses are distinguished from other enteroviruses by their pathogenicity
for suckling rather than adult mice. They are divided into 2 groups on the basis of
the lesions observed in suckling mice.
◦ Group A viruses produce a diffuse myositis with acute inflammation and
necrosis of fibers of voluntary muscles.
◦ Group B viruses produce focal areas of degeneration in the brain, necrosis in the
skeletal muscles, and inflammatory changes in the dorsal fat pads, the pancreas
and occasionally the myocardium.
Each of the 23 group A and 6 group B coxsackieviruses have a type specific antigen.
In addition, all from group B and one from group A (A9) share a group Ag. Cross-
reactivities have also been demonstrated between several group A viruses but no
common group antigen has been found.

15. Echoviruses
The first echoviruses were accidentally discovered in human faeces,
unassociated with human disease during epidemiological studies of
polioviruses. The viruses were named echoviruses (enteric, cytopathic,
human, orphan viruses).
These viruses were produced CPE in cell cultures, but did not induce
detectable pathological lesions in suckling mice.
Altogether, There are 32 echoviruses (types 1-34; echovirus 10 and 28
were found to be other viruses and thus the numbers are unused)
There is no group echovirus Ag but heterotypic cross-reactions occur
between a few pairs.

16. New Enteroviruses
Newly identified picornaviruses that are not polioviruses are no longer
classified separated into the species coxsackie and echovirus because of the
ambiguities presented by overlapping host range variations.
4 new enteroviruses have been identified (68 - 72). Enterovirus 70 is the
causative agent epidemics of acute haemorrhagic conjunctivitis that swept
through Africa, Asia, India and Europe from 1969 to 1974. The virus is
occasionally neurovirulent.
Enterovirus 71 appears to be highly pathogenic and has been associated with
epidemics of a variety of acute diseases, including aseptic meningitis,
encephalitis, paralytic poliomyelitis-like disease and hand-foot-mouth disease.
Enterovirus 72 was originally assigned to hepatitis A virus, but it had now
been assigned to a new family called heptoviruses.

17. Diseases associated with Enteroviruses