Virology

1. Enteroviruses
An Overview

2. Enteroviruses
 A genus of the picornavirus family
 Naked ssRNA virus
 Are stable in acidic pH
 Enter the body mainly via ingestion
 Primary site of replication is lymphoid
tissue in the gut.
 Spread to blood and into lumen of gut to
be excreted in feces

3. Enterovirus Particles
Courtesy of Linda M. Stannard, University of Cape Town, S.A.h

4.  At least 71 serotypes are known:
divided into 5 groups
 Polioviruses
 Coxsackie A viruses
 Coxsackie B viruses
 Echoviruses
 Enteroviruses
Enteroviruses

6. Poliovirus
 First identified in 1909
 First grown in cell culture in 1949 which
became the basis for vaccines.
 3 serotypes of poliovirus (1, 2, and 3)
but no common antigen.
 Humans are the only susceptible hosts.
 Polioviruses are distributed globally.
 Immunization has eradicated poliovirus
in most regions of the world except in
the Indian Subcontinent and Africa.

7. Pathogenesis
 Incubation period : 7 - 14 days.
 After ingestion, the virus multiplies
in the tonsils and Peyer's patches of
the ileum
 Transient viraemia occurs
 In few cases, involves the CNS
 Spreads along axons of peripheral
nerves to involve anterior horn cells
of spinal cord, intermediate grey
ganglia and even posterior horn cells

8. Poliomyelitis: Flaccid Paralysis

9. Clinical Manifestations
Subclinical infection (90 - 95%)
 A minor influenza-like illness
 Recovers within a few days
 May be accompanied by aseptic meningitis
Major illness (1 - 2%)
 Signs of aseptic meningitis.
 Infection of anterior horn cells: flaccid paralysis.
 Infection of medulla: respiratory paralysis and death.

10. Laboratory Diagnosis
 Virus Isolation
 Mainstay of diagnosis
 Can be readily isolated in cell culture
from throat swabs, feces, rectal swabs
& CSF.
 Serology
 Very rarely used

11. Support
for Polio
Patient

12. Prevention
No specific antiviral therapy is available.
 Intramuscular Poliovirus Vaccine (IPV)
 Formalin inactivated virus of all 3 serotypes.
 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.

13. Prevention
 The normal response rate to OPV is
close to 100%.
 OPV is used for the WHO poliovirus
eradication campaign.
 Poliovirus was targeted for eradication
by the WHO by the end of year 2005
 Eradicated from most regions of the
world except the Indian subcontinent
and sub-Saharan Africa.

14. Current Status of Wild Poliovirus Transmission

15. Properties of Enteroviruses
CPE in cell cultures
Monkey Human cell Pathology in
Group Virus types kidney culture newborn mice Major disease associations
Poliovirus 3 types + + - Paralytic poliomyelitis, aseptic
(1 - 3) meningitis, febrile illness.
Coxsackie 23 types - or E - or E + Aseptic meningitis,
group A (A1-22, A24) febrile illness, conjunctivitis
(A24), hand, foot and mouth disease.
Coxsackie 6 types + + + Aseptic meningitis, severe neonatal
group B (B1-6) disease, myopericarditis,
encephalitis, febrile
illness.
Echovirus 31 types + E - Aseptic meningitis, rash, febrile
(1-9, 11-27 illness, conjunctivitis, severe
29-33) generalized neonatal disease.
Enterovirus 5 types + + - Polio-like illness, aseptic
(68-72) meningitis, hand, foot and mouth
(E71), epidemic conjunctivitis (E70)
hepatitis A (E72)

16. Poliovirus Replication

17. Coxsackieviruses
 Coxsackieviruses are distinguished from other
enteroviruses by their pathogenicity for suckling rather
than adult mice.
 Two groups on the basis of the lesions in suckling mice.
 Group A: diffuse myositis with acute inflammation
and necrosis of fibers of voluntary muscles. Has 23
serotypes
 Group B: 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. Have 6 serotypes

18. Echoviruses
 Were accidentally discovered in human
feces, unassociated with human disease
during epidemiological studies of
polioviruses. The viruses were named
echoviruses (enteric, cytopathic, human,
orphan viruses).
 Altogether, There are 32 echoviruses
(types 1-9, 11-27, 29-34

19. New Enteroviruses
 Newly identified picornaviruses that are not
polioviruses, coxsackie, and echovirus : 5
types (68 - 72).
 Enterovirus 70 causes acute haemorrhagic
conjunctivitis
 Enterovirus 71 has been associated with
epidemics of aseptic meningitis, encephalitis,
paralytic poliomyelitis-like disease and
hand-foot-mouth disease.

20. Diseases associated with Enteroviruses
Syndrome Polio Cox A Cox B Echo
Paralytic disease + + + +
Meningitis-encephalitis + + + +
Carditis + + + +
Neonatal disease - - + +
Pleurodynia - - + -
Herpangina - + - -
Rash disease - + + +
Haemorr. conjunctivitis - + - -
Respiratory infections + + + +
Undifferentiated fever + + + +
Diabetes/pancreatitis - - + -

21. Laboratory Diagnosis
 Virus Isolation
 Mainstay of diagnosis of enterovirus infection
 Coxsackie B and Echoviruses can be readily grown in cell culture from
throat swabs, feces, and rectal swabs. They can also be isolated from the
CSF
 Coxsackie A viruses cannot be easily isolated in cell culture. Can be
isolated readily in suckling mice. Molecular techniques may provide a
better alternative.
 Serology
 Very rarely used for diagnosis since cell culture is efficient.
 Neutralization tests or EIAs

22. Cytopathic Effect
(Virology Laboratory, New-Yale Haven Hospital)

23. Management and Prevention
 No specific antiviral therapy available
 IVIG in the treatment of neonatal
infections or severe infections in
immunocompromised individuals.
 HNIG to prevent outbreaks of
neonatal infection with good results.
 No vaccine available