Enteroviruses

Family Picornaviridae
Genus Main syndromes
Enterovirus Infections of the CNS,
heart, skeletal muscles,
skin and mucous
membranes
Hepatovirus Hepatitis A

Rhinovirus Common cold

Aphthovirus Foot and mouth disease of

animals

Cardiovirus Encephalitis and myocarditis

Parechovirus Diarrhoea

Replicate in the gut but gastroenteritis is however not a major

feature of picornavirus infections
Members of the genus enterovirus that infect
humans

Group No of serotypes
Polio virus 3

Coxsackie virus A 23

Coxsackie virus B 6

Echo virus 32

Enterovirus 5 ( 68-72)
 Picornaviridae structure

The virion of enterovirus consists of a capsid shell of 60

subunits
each of four proteins(vp1-vp4)arranged with icosahedral
symmetry around a genome made up of a single strand of
positive sense RNA
 Picornavirus: Morphology

27nm, icosahedral symmetry, no envelope

Genome organisation
 Poliovirus

Poliovirus may cause

poliomyelitis , which is an
infectious disease that in its
serious form affects the central
nervous system. However,
most poliovirus infections are
subclinical.
Human are the only known
reservoir of infect-ion.
Polio remains endemic in three countries Afghanistan,
Nigeria and Pakistan.
 Polio virus life cycle
• Poliovirus infection occurs by ingestion of contaminated material via the
gastrointestinal mucosal surfaces .
• Suitable host cells are targeted if they express CD155, the only known
receptor for poliovirus.
• Particle internalized by endocytosis then the RNA is released into the cell
cytoplasm.
• An internal ribosome entry site (IRES) recruits cellular ribosomes and one
large polypeptide is first translated
• Polypeptide cleaved into component virus proteins:
✓ P1; structural proteins vp1, vp2, vp3, vp4
✓ P2; non structural proteins including protease
✓ P3; RNA polymerase and other proteins
• Production of RNA polymerase allows for initiation of genome replication
• Assembly of viral nucleic acid and structural proteins takes place in the
cytoplasm
 Effect on host cell translation
• Virus uses host cell translational machinery
• Virus inhibits host cell “cap-dependent” translation
• poliovirus 2A protease cleaves eIF4G component of eIF4F complex
• eIF4F = 4G, 4E and 4A
• Virus uses alternative translation mechanism; IRES
• The cell normally dies after a viral replication period of 4Hrs and
about 1million virus particles are released by cell death and lysis.

40S
PV 2A

4G
4A
4E
POLIO: Pathogenesis ﹠ Pathology:
 POLIO: Pathogenesis ﹠ Pathology:
• The virus first multiplies in throat, tonsil ( lymph nodes of the neck), Peyer ’ s
paches (small intestine)
• the virus gains access to the brain by infecting skeletal muscle and traveling
up the innervating nerves to the brain, similar to the rabies virus.
• The virus is cytolytic for the motor neurons of the anterior horn and
brainstem. The location and number of nerve cells destroyed by the virus
govern the extent of paralysis and whether and when other neurons can
reenervate the muscle and restore activity.
• Polio (poliomyelitis) mainly affects children under 5 years of age.
• Among those paralysed, 5% to 10% die when their breathing muscles
become immobilized.
• The combined loss of neurons to polio and to old age may result in
paralysis later in life, termed postpolio syndrome.
 POLIO: Clinical Manifestations
• The incubation period: 4 days or as long as 35 days
• Most infections asymptomatic, 95%

• Abortive polio (minor illness), 5%: fever, malaise, sore throat,

myalgia, headache, vomiting)

• Aseptic meningitis (non paralytic polio), 1%; (stiff neck,

sensitivity to light : meningitis) concludes within a week

• Irreversible Paralytic polio (major illness), 0.1- 1%: flaccid

paralysis ; Lower, or upper extremities, bulbar.
Involvement : spinal cord anterior horn cells, motor cortex, dorsal
root ganglia
bulbar: involvement of cranial nerves results in paralysis of pharynx
Among those paralysed, 5% to 10% die when their breathing muscles
become immobilized.
Child with polio sequelae
Immunity:
Immunity is permanent to the type cau-
sing the infection.
Passive immunity is transferred from
mother to offspring, which gradually
disappear during the first 6 months of
life.
 Laboratory Diagnosis
• Specimen: throat swabs, feces, CSF,blood
• Virus Isolation
– Mainstay of diagnosis of poliovirus infection. Poliovirus is
most likely to be isolated from stool specimens. It may
also be isolated from pharyngeal swabs. Isolation is less
likely from blood or CSF.
– Human or monkey used: only primate cells possess
specific receptors
– CPE: Rounded, shrunken cells with altered nuclei , and
eventually complete destruction of the cell line
• Serology; detection of antibodies
• A rising titer of Antibody in paired sera taken early in infection and
10-14 days later is good evidence of infection
• IgM antibody capture ELISA
• Detection of viral genome: reverse transcriptase PCR ( rtPCR)
Prevention ﹠ control:
• Both live-virus and killed-virus vaccines are avail-able .
They induce antibody and protect the central nervous
system from subsequent invasion by wild virus.
• A potential limiting factor for oral ( life att) vaccine
is :vaccine-associated disease,
• a switch to the use of only inactivated poliovaccine (four
doses) for children has been proposed esp if they are
immune compromised
• Immune globulin can provide protection for a few weeks
against the paralytic disease but does not prevent
subclinical infection.
 Vaccines Available
• Intramuscular Poliovirus Vaccine (IPV)
– consists of formalin inactivated virus of all 3 poliovirus serotypes (Salk)
– 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 (Sabin).
– 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

❖ There is no cure for polio, it can only be prevented. Polio vaccine, given
multiple times, can protect a child for life.
Live virus generates a more complete immune response

Killed Live .Att (Sabin)

(Salk) Vaccine Serum
51 Serum
Vaccine IgG
2 IgG

12
8
Reciprocal virus antibody titer

32
Serum IgM Serum
IgM Nasal
Serum IgA
8
IgA
Serum
2 IgA
Nasal and Duodenal
duodenal IgA IgA
1
4 96 48 9
8 6
Vaccination Days Vaccination
Circulating vaccine-derived poliovirus
type 2 (cVDPV2)
 Circulating vaccine-derived poliovirus type 2
(cVDPV2)
• VDPV2: A strain of poliovirus mutated from the strain originally
contained in OPV (oral polio vaccine).
• OPV contains a live, weakened form of poliovirus that replicates in
the intestine
• On rare occasions, when replicating in the GI, OPV strains
genetically change and may spread in communities that are not
fully vaccinated against polio,
• the vaccine-derived virus can genetically change into a form that
can cause paralysis as does the wild poliovirus – this is what is
known as a vaccine-derived poliovirus (VDPV)

• RISK factors: poor hygiene, poor sanitation, or overcrowding.

• The lower the population immunity, the longer this virus survives
and the more genetic changes it undergoes.

Novel Oral Polio Vaccine type 2 (nOPV2):more genetically stable than Sabin oral
poliovirus vaccines, and, therefore, reduces the risk of type 2 circulating vaccine-derived
polioviruses (cVDPV2)
• 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
 Key facts: WHO

• Polio (poliomyelitis) mainly affects children under 5 years of age.

• One in 200 infections leads to irreversible paralysis. Among those
paralysed, 5% to 10% die when their breathing muscles become
immobilized.
• Polio cases have decreased by over 99% since 1988,
• from an estimated 350 000 cases then, to 406 reported cases in 2013. The
reduction is the result of the global effort to eradicate the disease.
• In 2014, only 3 countries (Afghanistan, Nigeria and Pakistan) remain polio-
endemic, down from more than 125 in 1988.
• As long as a single child remains infected, children in all countries are at
risk of contracting polio. Failure to eradicate polio from these last
remaining strongholds could result in as many as 200 000 new cases every
year, within 10 years, all over the world.
• In most countries, the global effort has expanded capacities to tackle
other infectious diseases by building effective surveillance and
immunization systems.
 Enteroviruses

▪ Poliovirus
▪ Coxsackie viruses
▪ ECHOvirus
 Pathogenic mechanism

▪ enteroviruses are characterized by their ability to cause

(cytopathic effects)CPE in tissue culture and by their
capacity to initiate acute disease by inducing apoptosis
within targeted organs in vivo. So,these viruses are
considered highly cytolytic.
▪ Tissues damage also result from immune meadiated cell
death: lysis of infected cells by CD8+T cells
▪ Inflammation
coxsackievirus and ECHO virus
▪ Late summer or early fall…It’s not yet cold or flu season,
but your child is sick. Consider coxsackievirus or ECHO
virus.
▪ It’s often the culprit when parents leave a doctor’s
appointment without knowing what disease their child has.
▪ Coxsackieviruses and ECHO viruses, are enteroviruses.
These viruses share in common that they infect the human
intestines (and stool), but they can cause symptoms
throughout the body.
▪ many enteroviruses, may be associated with pyrexial
illness- the so-called summer grippe, with sore throat,
cough, or coryza.
 CV groups
▪ Coxsackieviruses are divided into two groups,
denoted A and B, based on early findings that
each produced a different degree of paralysis in
mice (CVA induce flaccid paralysis, while CVB
induce spastic paralysis).
▪ There are twenty-three known serotypes of
coxsackievirus A
▪ 6 serotypes of coxsackievirus B
 Incubation
▪ The incubation period (the time
between infection and the onset of
symptoms) for most coxsackie
virus infections is about 2 to 10
days
Hand-foot-and-mouth disease
▪ conjunctivitis
Echo virus pathogenesis
 ECHO virus rash
Enteric cytopathic human orphan (ECHO) viruses.
▪ Skin rashes are more common with EV infections
than with infections from other enteroviruses
▪ Likelihood of an exanthem being present appears
directly related to the EV type causing infection.
▪ Skin findings with EV infections are self-limited
and without sequelae.
Review