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Picornaviruses

By :
Farhang Shapouran

Supervisor:
Dr. Mojtaba Fattahi
Associate Professor of Medical Virology

Sabzevar University of Medical Sciences

Nov.2019
 Picornaviruses
 As the name indicates, these viruses are small (Pico) ribonucleic acid (RNA) viruses that h
ave a naked capsid structure.

 Very large virus family with respect to the number of members

 One of the smallest in terms of virion size and genetic complexity.

 They include two major groups of human pathogens:

1.Enteroviruses and
2.Rhinoviruses.

 Less common picornaviruses associated with human illness include hepatitis A virus, parec
hovirus , cardiovirus , and Aichi virus.

 Many picornaviruses cause diseases in humans ranging from severe paralysis to aseptic me
ningitis, pleurodynia , myocarditis, vesicular and exanthematous skin lesions , mucocutane
ous lesions, respiratory illnesses, undifferentiated febrile illness, conjunctivitis, and severe
generalized disease of infants. However, subclinical infection is far more common than cli
nically manifest disease.
 Picornaviruses

 Properties of Picornaviruses
 Genus Enterovirus
 Polioviruses
 Coxsackieviruses
 Other Enterovirus
 Enteroviruses in the Environment
 Rhinoviruses Species
 Genus Parechovirus
 Genus Aphthovirus
 Genus Hepatovirus (Explained at Hepatitis season)
 References
Properties of Picornaviruses

 Structure and Composition

 Classification

 Replication
 Structure and Composition

 Virion: Icosahedral, 28–30 nm in diameter, capsid shell of 60 subunits

 Composition: RNA (30%), protein (70%)

 Genome: Single-stranded RNA, linear, positive sense, 7.2–8.4 kb in size, molecular weight 2.5 milli
on, infectious, contains genomelinked protein (VPg)

 Proteins: Four major polypeptides cleaved from a large precursor polyprotein. Surface capsid protei
ns VP1 and VP3 are major antibody-binding sites. VP4 is an internal protein.

 Envelope: None

 Replication: Cytoplasm

 Outstanding characteristic: Family is made up of many enterovirus and rhinovirus types that infect
humans and lower animals, causing various illnesses ranging from poliomyelitis to aseptic meningiti
s to the common cold.
 Structure and Composition
• Each of four proteins (VP1–VP4) arranged with icosahedral symmetry around a genome
made up of a single strand of positive-sense RNA . Parechoviruses are similar except that
their capsids contain only three proteins because VP0 does not get cleaved into VP2 and
VP4.

• The genome RNA ranges in size from 7.2 kb (human Rhinovirus) to 7.4 kb (poliovirus, h
epatitis A virus) to 8.4 kb (aphthovirus).

• The genome is polyadenylated at the 3′end and has a small viral-coded protein (VPg) cov
alently bound to the 5′ end. The positive-sense genomic RNA is infectious.

• Whereas enteroviruses are stable at acid pH (3.0–5.0) for 1–3 hours, rhinoviruses are acid
labile. Enteroviruses and some rhinoviruses are stabilized by magnesium chloride against
thermal inactivation.
Famil Specie
Classification
y
Genus
s

Enteroviru
s
Enterovirus
Rhinovirus
Hepatovirus

BovineRhinitis
Cardiovirus A

BovineRhinitis
Picornaviridae Aphtovirus B

Foot and
Mouth
Disease

Parechovirus A…D

Aichivirus
Kubovirus A…F
 Classification

Entrovirus

Coxsackieviru
s Poliovirus Enterovirus Echovirus

100 Types
B 1-3 31 Types
A A…J
1-22 ,24 1-6

Hepatovirus Rhinovirus

B…I A C B A
(HAV) 1-56 1-104 1-108
 Replication

 The picornavirus replication cycle occurs in the cytoplasm of cells .First, the virion attaches to a spe
cific receptor in the plasma membrane.

 Receptor binding triggers a conformational change in the virion which results in release of the viral
RNA into the cell cytosol.

 eIF4 is often cleaved by a viral protease, leading to shut-off of host protein synthesis and preferential
translation of viral RNAs.

 The infecting viral RNA strand is copied, and that complementary strand serves as template for the s
ynthesis of new plus strands.

 The mature virus particles are released when the host cell disintegrates.

 The multiplication cycle for most picornaviruses takes 5–10 hours.

Enterovirus Group

 Polioviruses
 Coxsackieviruses
 Other Enterovirus
 Enteroviruses in the Environment
Polio
viruses
 Properties of the virus
1) General Properties :

• An acute infectious disease.

• In it’s serious affects the CNS (Destruction of motor neurons in the spinal cord)
• Most poliovirus infections are subclinical.
• Poliovirus has served as a model enterovirus in many laboratory studies of the molecular biology of picornavirus r
eplication.
• Inactivated at 55°C for 30 minutes , while Mg2+, 1 mol/L, prevents this inactivation.
• Whereas purified poliovirus is inactivated by a chlorine concentration of 0.1 ppm , are required to disinfect sewage
containing virus in fecal suspensions .
 PolioViruses

2) Animal Susceptibility and Growth of Virus

•Poliovirus requires a primate-specific membrane receptor for infection, and the absenc
e of this receptor on the surface of nonprimate cells makes them virus resistant .

•This restriction can be overcome by transfection of infectious poliovirus RNA into res
istant cells.

•Introduction of the viral receptor gene converts resistant cells to susceptible cells.

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 PolioViruses
Pathogenesis and Pathology

•The mouth is the portal of entry of the virus, and primary multiplication takes place
in the oropharynx or intestine.

•regularly present in the throat and in the stools before the onset of illness.

•virus continues to be excreted in the stools for several weeks even though high
antibody levels are present in the blood.

•may be found in the blood of patients with nonparalytic poliomyelitis.

•Antibodies to the virus appear early in the disease, usually before paralysis occurs.

•the virus first multiplies in the tonsils, the lymph nodes of the neck, Peyer’s patches,
and the small intestine. The CNS may then be invaded by way of the circulating blood.

•In addition to pathologic changes in the nervous system, there may be myocarditis,
lymphatic hyperplasia, and ulceration of Peyer’s patches.
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 PolioViruses
 Clinical Findings

•Most infections are subclinical; only about 1% of infections result in clinical illness.
•The incubation period is usually 7–14 days, but it may range from 3 to 35 days.
o Mild Disease
most common form
fever, malaise, drowsiness ,headache , nausea, vomiting, constipation, and sore throat
Recovery in a few days
o Nonparalytic Poliomyelitis (Aseptic Meningitis)
In addition , stiffness and pain in the back and neck
Recovery within 2-10 days
Only one of many viruses that produce aseptic meningitis
small percentage advanced to paralysis
o Paralytic Poliomyelitis
The predominating complaint is flaccid paralysis from lower motor neuron damage.
Maximal recovery within 6 mounths
o Progressive Postpoliomyelitis Muscle Atrophy
Has been observed in individuals decades after their experience with paralytic poliomyelitis.
Rare
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 PolioViruses
 Epidemiology
• Before global eradication efforts began, poliomyelitis occurred worldwide—year-round in t
he tropics and during summer and fall in the temperate zones. Winter outbreaks were rare.
• Children are usually more susceptible )acquired immunity of Adults)
• fatality rate is highest in oldest patients.
• Humans are the only known reservoir of infection.
 Prevention and Control
• Both live-virus and killed-virus vaccines
• Killed-virus vaccine induces humoral antibodies but does not induce local intestinal immun
ity so that virus is still able to multiply in the gut.
• Live-virus vaccine produces not only immunoglobulin M (IgM) and IgG antibodies in the b
lood but also secretory IgA antibodies in the intestine, enabling mucosal immunity.
• After global eradication is achieved, the use of oral polio vaccine will cease. Continuation o
f its use could lead to the reemergence of polio caused by mutation.
• Ig can’t prevent subclinical infection.
• Ig is effective only if given shortly before infection; it is of no value after clinical symptom
s develop.
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Coxsackie
viruses
 Properties of the virus
1) General Properties : classified into HEV groups A, B, and C

 They produce a variety of illnesses in humans, including:

 aseptic meningitis and respiratory and undifferentiated febrile illnesses.
 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, and severe generalized disease of infants are caused
by some group B coxsackieviruses.
 A number of group A and B serotypes can give rise to meningoencephalitis and paralysis.
 Generally, paralysis produced by nonpolio enteroviruses is incomplete and reversible.
 Coxsackie B viruses are the most commonly identified causative agents of viral heart disease in humans .
 The coxsackieviruses tend to be more pathogenic than the echoviruses.
 Coxsackieviruses
 Pathogenesis and Pathology

• Virus has been recovered from the blood in the early stages of natural infection in humans
.
• Virus is also found in the throat for a few days early in the infection and in the stools for u
p to 5–6 weeks.

 Clinical Findings

• The incubation period ranges from 2 to 9 days.

• Although the gastrointestinal tract is the primary site of replication for enteroviruses, the
y do not cause marked disease there .
• A number of coxsackieviruses have been associated with common colds and with undiff
erentiated febrile illnesses.

• Aseptic meningitis is caused by all types of group B and by many group A .The dise
ase sometimes progresses to mild muscle weakness suggestive of paralytic poliomyel
itis.

• Herpangina is a severe febrile pharyngitis that is caused by certain group A viruses.

The illness is self-limited and most frequent in small children . 17
 Coxsackieviruses
 Clinical Findings

• Hand-foot-and-mouth disease is characterized by oral and pharyngeal ulcerations a

nd a vesicular rash of the palms and soles that may spread to the arms and legs. Vesic
les heal without crusting, which clinically differentiates them from the vesicles of her
pesviruses and poxviruses. Virus may be recovered not only from the stool and phary
ngeal secretions but also from vesicular fluid.

• Pleurodynia (also known as epidemic myalgia) is caused by group B viruses. Fever

and stabbing chest pain are usually abrupt in onset. The illness is self-limited and rec
overy is complete, although relapses are common.
• Myocarditis is an acute inflammation of the heart or pericarditis. Infections may be
fatal in neonates or may cause permanent heart damage at any age.

• Generalized disease of infants is an extremely serious disease caused by group B co

xsackieviruses. in which the infant is overwhelmed by simultaneous viral infections o
f multiple organs of visceral , including the heart, liver, and brain. The clinical course
may be rapidly fatal, or the patient may recover completely.

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 Coxsackieviruses
 Epidemiology

• Viruses of the coxsackie group have been encountered around the globe. Isolations have be
en made mainly from human feces, pharyngeal swabbings, and sewage.

 Prevention and Control

• There are no vaccines or antiviral drugs currently available for prevention or treatment of di
seases caused by coxsackieviruses;
• Symptomatic treatment is given.

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Other
Enterovirus
• Echoviruses (enteric cytopathogenic human orphan viruses), based on historical terminology, were grouped together
because they infect the human enteric tract .

 Clinical Findings

• Many echoviruses have been associated with aseptic meningitis.

• Rashes are most common in young children.
• For many echoviruses, no disease entities have been defined.
• Enterovirus 70 is the chief cause of acute hemorrhagic conjunctivitis. most common in adults, with an incubat
ion period of 1 day and a duration of 8–10 days. Complete recovery is the rule.
• Enterovirus 71 has been isolated from patients with meningitis, encephalitis, and paralysis resembling poliomy
elitis. One of the main causes of CNS disease, sometimes fatal, around the world.
 Other Enterovirus
 Epidemiology

• They occur in all parts of the globe and are more apt to be found in younger than in older
individuals.
• infections occur chiefly in the summer and autumn .

 Control

• Avoidance of contact with patients exhibiting acute febrile illness is advisable for very y
oung children.
• There are no antivirals or vaccines (other than polio vaccines) available for the treatmen
t or prevention of any enterovirus diseases.

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Enteroviruses
in the Environment

• Humans are the only known reservoir for members of the human enterovirus group.

• These viruses are generally shed for longer periods of time in stools than in secretions from the upper alimentary
tract.

• Enteroviruses survive exposure to the sewage treatments and chlorination in common practice.
 Enteroviruses
in the Environment

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Rhinoviruses Species

Genus Parechovirus

Genus Aphthovirus
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 Rhinoviruses

• Common cold viruses

• Most commonly recovered agents from people with mild upper respiratory illnesses
• Also responsible for about half of asthma exacerbations

Properties of the Virus

• more thermostable than other enteroviruses

• infectious only for humans, gibbons, and chimpanzees.
• Most grow better at 33°C, which is similar to the temperature of the nasopharynx i
n humans, than at 37°C.

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 Rhinoviruses
Pathogenesis and Pathology

• Enters via the upper respiratory tract

• High titers of virus in nasal secretions—which can be found as early as 2–4 days after e
xposure—are associated with maximal illness.
• Replication is limited to the surface epithelium of the nasal mucosa.
• Rhinoviruses rarely cause lower respiratory tract disease in healthy individuals.

Clinical Findings

• The incubation period is brief—from 2 to 4 days—and the acute illness usually lasts for
7 days, although cough may persist for 2–3 weeks.
• The average adult has one or two attacks each year.
• Secondary bacterial infection may produce acute otitis media, sinusitis, bronchitis, or p
neumonitis, especially in children

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 Rhinoviruses
Immunity

• Antibody develops 7–21 days after infection.

• Because recovery from illness usually precedes appearance of antibody, it seems that
recovery is not dependent on antibody. However, antibody may accomplish final clearance o
f infection.
• Serum antibody persists for years but decreases in titer.

Epidemiology

• occurs throughout the world

• the attack rates are highest in early fall and late spring
• The virus is believed to be transmitted through close contact by means of virus contaminated
respiratory secretions. The fingers of a person with a cold are usually contaminated.
• Infection rates are highest among infants and children and decrease with increasing age.

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 Rhinoviruses
Treatment and Control

• No specific prevention method or treatment is available.

• The development of a potent rhinovirus vaccine is unlikely because of the difficulty in g

rowing rhinoviruses to high titer in culture, the fleeting immunity, and the multiplicity of
serotypes causing colds.

• Many compounds effective in vitro have failed to be effective clinically.

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 Parechovirus
Properties of the Virus

• Parechoviruses are highly divergent from enteroviruses, with no protein sequence having
greater than 30% identity with the corresponding protein of other picornaviruses.

• The capsid contains three proteins because the VP0 precursor protein does not get cleave
d.

• Infections are often acquired in early childhood.

• replicate in the respiratory and gastrointestinal tracts.

• cause diseases similar to other enteroviruses, such as mild gastrointestinal and respirator
y illness, meningitis, and neonatal sepsis.

• Human parechovirus 1 was one of the 15 most common enterovirus detections from 200
6 to 2008.
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 Aphthovirus
Properties of the Virus

• This highly infectious disease of cloven-hoofed animals such as cattle, sheep, pigs, and
goats.

• In humans, the disease is characterized by fever, salivation, and vesiculation of the

mucous membranes of the oropharynx and of the skin of the feet.

• in animals is highly contagious in the early stages of infection when viremia is present a
nd when vesicles in the mouth and on the feet rupture and liberate large amounts of viru
s.

• Excreted material remains infectious for long periods. all exposed animals are slaughtere
d and their carcasses destroyed .

• The mortality rate in animals is usually low but may reach 70%.

• A variety of animals are susceptible to infection, and the virus has been recovered from
at least 70 species of mammals. 30
 Aphthovirus
Properties of the Virus

• Formalin-treated vaccines have been prepared from virus grown in tissue cultures, but su
ch vaccines do not produce long-lasting immunity.

• New vaccines are being developed based on recombinant DNA techniques.

• Strict quarantine is established, and the area is not presumed to be safe until susceptibl
e animals fail to develop symptoms within 30 days.

• Another method is to quarantine the herd and vaccinate all unaffected animals. (systemat
ic vaccination schedules )

• Some nations (eg, the United States and Australia) forbid the importation of potentially i
nfective materials such as fresh meat, and the disease has been eliminated in these areas.

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 References

 Jawetz, Melnick, & Adelberg’s

Medical Microbiology
27th. Edition

 Murray, Patrick R.
Medical Microbiology
8th. Edition

 International Committee on Taxonomy of

Viruses(ICV)