3. PIcornavIruses
Picornaviruses represent a very large virus family with respect to
the number of members but one of the smallest in terms of
virion size and genetic complexity. They include two major
groups of human pathogens: enteroviruses and rhinoviruses.
Many picornaviruses cause diseases in humans ranging from
severe paralysis to aseptic meningitis, pleurodynia,
myocarditis, vesicular and exanthematous skin lesions,
mucocutaneous lesions, respiratory illnesses, undifferentiated
febrile illness, conjunctivitis, and severe generalized disease of
infants.
4. The most serious disease caused by any enterovirus is
poliomyelitis.
5. +ProPerTIes
Structure and composition
30 nm, icosahedral
plus-strand RNA, 7.2-8.4 kb
RNA is poly adenylated
VP1, VP2, VP3, VP4 structural proteins
VP4 interacts with viral RNA
2A, 2B, 2C proteases
3A, 3B, 3C, 3D RNA replication
Nonenveloped
Cytoplasmic replication
Resistant to pH 3 to 9 (except forResistant to pH 3 to 9 (except for
Rhinoviruses).Rhinoviruses).
6. PIcornavIrus sTrucTurePIcornavIrus sTrucTure
The Basic capsid building block is a protomer that consists of one copy
each of VP1, VP2, VP3 & VP4. VP1, VP2 & VP3 are on the virion
surface, with VP4 being internal. VP1, VP2 & VP3 have no sequence
homology, but have the same topology.
VP1
VP2
VP3
5-fold
Axis
3-fold
Axis
2-fold
Axis
7. PIcornavIrus sTrucTurePIcornavIrus sTrucTure
The genome of the picornaviruses resembles a messenger RNA (mRNA).
It is a single strand of plus-sense RNA of approximately 7200 to 8450
bases that has a poly A at the 3/-end and a small protein.VPg (22 to 24
amino acids). attached to the 5-'end. The poly A sequence enhances the
infectivity of the RNA. And the VPg may be important in packaging the
genome into the capsid and initiating viral RNA synthesis. Tile naked
picornavirus genome is sufficient to infect a cell.
9. rePlIcaTIon
Rapid replication in the cytoplasmbecause infecting viral RNA is
equal to mRNA
A precursor polyprotein is translated and processed by viral
enzymes.
Synthesis of new viral (+) RNA is through a complementary (-)
strand.
Nucleocapsids are assembled and released by lysis.
As many as 100.000 virions per cell may be produced and released
on cell lysis.
11. A single type of receptor mediates virus Human Rhinovirus
binding and entry
The integral membrane protein, intercellular adhesion molecule 1
(Icam-1) was identified as the receptor for the major group of
human rhinoviruses.
Icam-1 is a member of the immunoglobulin superfamily.
Icam -1 is found on the surface of many tissues, including nasal
epithelium and lung epithelium.
The normal function of Icam-1 is to bind a ligand on the surface of
lymphocytes and to promote immunological and inflammatory
functions.
This host response accounts in part for cold symptoms.
14. Functions oF viral Proteins
Derived from one polyprotein precursor
Processed by post-translational cleaving
Structural proteins
responsible for host tropisms
protection of genome
antigenicity
Non-structural proteins
proteases
RNA polymerase
inhibitors of normal host cell functions
16. enterovirus Diseases
Spread by fecal-oral route
Grow initially in the GI mucosa.
Most infections are sub-clinical.
Can cause a variety of severe diseases :
meningitis, paralysis disease, myalgia, hand-foot-and
mouth disease, herpangina, pericarditis, myocarditis,
pleurodynia exanthems, colds, diarrhea
17. PatHoGenesis anD iMMunity
Contrary to their name. enteroviruses do not usually cause enteric disease
but are transmitted by the fecal-oral route.
Most enteroviruses are cytolytic. replicating rapidly and causing direct
damage to the target cell. The hepatitis A virus is the exception because it
is not very cytolytic.The kinetics of the immune response to hepatitis A
correlate with the appearance of symptoms. Indicating
immunopathogenesis.
Antibody is the major protective immune response to the
Enteroviruses.
Cell-mediated immunity is not usually involved in protection
but may playa role in pathogenesis.
19. Poliovirus
3 serotypes of poliovirus (1, 2, and 3) but no common antigen.
Identical physical properties but only share 36-52% nucleotide homology.
Humans are the only susceptible hosts.
Distributed globally. Before the availability of immunization, almost 100%
of the population in developing countries before the age of 5.
Immunization campaign has eradicated poliovirus in most regions of the
world except in the Indian Subcontinent and Africa.
20. 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, is invaded and the virus enters the blood resulting in a transient
viremia.
In a minority of cases,the virus may involve the C NS following
dissemination.
22. HuMan PolioMyelitis
1. Fecal/oral route of entry
2. Infect cervical and small intestine
lymph nodes
3. Not inactivated by pH 3.0
4. Viremia; virus infects epithelium of
large intestine
5. Infects Peyer’s patches
6. Viremia; pass through blood brain
barrier
7. Infects anterior horn cells of motor
neurons in spinal cord causing flaccid
paralysis
8&9. Infects brain causing tissue
damage---affects breathing; bulbar
polio
10. Virus shed in feces
23. CliniCal Findings
When an individual susceptible to infection is exposed to the
virus, the response ranges from inapparent infection without
symptoms, to a mild febrile illness, to severe and permanent
paralysis.
• Poliovirus may cause one of the following four outcomes in
unvaccinated people. depending on the progression of the
infection:
24. CliniCal Findings
A. ABORTIVE POLIOMYELITIS;
This is the most common form of the disease. The patient has
only the minor illness, characterized by fever, malaise,
drowsiness, headache, nausea, vomiting, constipation, and sore
throat in various combinations. Recovery occurs in a few days.
25. CliniCal Findings
B. NONPARALYTICPOLIOMYELITIS
(ASEPTICMENINGITIS);
In addition to the symptoms and signs listed in the preceding
paragraph, the patient with the non paralytic form has stiffness
and pain in the back and neck. The disease lasts 2-10 days, and
recovery is rapid and complete. In a small percentage of cases,
the disease advances to paralysis. Poliovirus is only one of
many viruses that produce aseptic meningitis.
26. CliniCal Findings
C. PARALYTIC POLIOMYELITIS;
The predominating complaint is flaccid paralysis resulting from
lower motor neuron damage. However, incoordination
secondary to brain stem invasion and painful spasms of non
paralyzed muscles may also occur. The amount of damage
varies greatly. Maximal recovery usually occurs within 6
months, with residual paralysis lasting much longer.
27. CliniCal Findings
D. PROGRESSIVE POSTPOLIOMYELITIS MUSCLE
ATROPHY;
A recrudescence of paralysis and muscle wasting has been
observed in individuals decades after their experience with
paralytic poliomyelitis. Although progressive
postpoliomyelitis muscle atrophy is rare, it is a specific
syndrome.
28. vaCCine
The two types of poliovirus vaccine are:
1- inactivated polio vaccine (lPV). developed by Jonas Salk.
2- live attenuated oral polio vaccine (OPV). developed by Albert Sabin.
29. global eradiCation
A major campaign by the World Health Organization is under
way to eradicate poliovirus from the world as was done for
smallpox virus. The Americas were certified as free from wild
poliovirus in 1994, the Western Pacific Region in 2000, and
Europe in 2002. Progress is being made globally, but several
thousand cases of polio still occur each year, principally in
Africa and the Indian subcontinent.
30. CoXsaCKievirUses
Coxsackieviruses, a large subgroup of the enteroviruses,are
divided into two groups, A and B.
Herpangina (vesicular pharyngitis), hand-foot-and-mouth
disease, and acute hemorrhagic conjunctivitis are caused by
certain coxsackievirus group A serotypes.
pleurodynia (epidemic myalgia), myocarditis, pericarditis,
meningoencephalitis, and severe generalized disease of infants
are caused by some group B coxsackieviruses.
31. CliniCal Findings
The incubation period of coxsackievirus infection ranges from 2
days to 9 days.
Aseptic meningitis;
is caused by all types of group B coxsackieviruses and by many
group A coxsackieviruses, most commonly A7 and A9. Fever,
malaise, headache, nausea, and abdominal pain are common
early symptoms.
32. CliniCal Findings
Herpangina;
is a severe febrile pharyngitis. It is caused by certain group A
viruses. Despite its name, it has nothing to do with
herpesviruses.
33. CliniCal Findings
Hand-foot-and-mouth;
disease is characterized by oral and pharyngeal ulcerations and a
vesicular rash of the palms and soles that may spread to the
arms and legs. This disease has been associated particularly
with coxsackievirus AI6, but A5 and A10 have also been
implicated.
34. CliniCal Findings
Pleurodynia (also known as epidemic myalgia or Bornholm
disease);
is caused by group B viruses. Fever and stabbing chest pain are
usually abrupt in onset but are sometimes preceded by
malaise, headache, and anorexia.
Myocarditis;
is a serious disease. It is an acute inflammation of the heart or its
covering membranes (pericarditis). Coxsackievirus B
infections are a cause of primary myocardial disease in adults
as well as children. about 5% of all symptomatic
coxsackievirus infections induce heart disease. Infections may
be fatalin neonates or may cause permanent heart damage at
any age.
35. EpidEmiology
Viruses of the coxsackie group have been encountered around the
globe. Isolations have been made mainly from human feces,
pharyngeal swabbings, sewage, and flies.
Coxsackieviruses are recovered much more frequently in summer
and early fall.
Control:
There are no vaccines or antiviral drugs currently available for
prevention or treatment of diseases caused by
coxsackieviruses.
36. RhinoviRusEs
Rhinoviruses are the most important cause of the common
cold and upper respiratory tract infections.
Such infections are self-limited, however, and do not cause
serious disease.
37. RhinoviRus pathogEnEsis
localized infections of the nose.
responsible for most cases of the common cold.
more heat and acid labile than the enteroviruses.
symptoms occur 2 to 4 days after exposure and last about one week. There
is no fever.
Transmission is by contact with respiratory secretions (e.g. air, hands, door
handles, inanimate objects)
39. hEpatitis a viRus
Hepatitis A, which is sometimes known as infectious hepatitis:
1- is caused by a picornavirus. a ribonucleic
acid (RNA) virus.
2- is spread by the fecal-oral route.
3- has an incubation period of approximately 1 month, after
which icteric symptoms start abruptly.
4- does not cause chronic liver disease.
5- rarely causes fatal disease.
