PICORNAVIRUS

PROPERTIES
• The smallest RNA viruses (24-30 nm)
• Non-enveloped icosahedrons
• Capsid consists of 4 different antigenic polypeptides
• RNA is single-stranded, and of positive (message) sense
• Viruses replicate rapidly in the cytoplasm
• Largest and important family of viral pathogens
 CLASSIFICATION
Genus Enterovirus - Diseases of the human (and other) alimentary tract
• Polio, types 1-3
• Coxsackie A , types 1-24
• Coxsackie B, types 1-6
• Echo, types 1-34
• Other enteroviruses, types 68-71
Genus Rhinovirus - cause respiratory tract infections
Genus Hepatovirus - Hepatitis A, contagious liver infections.

Genus Cardiovirus-cause heart and brain inflammation

Genus Apthovirus - Foot and mouth disease, most destructive in Africa
 STRUCTURE
• The virus capsid is composed of 60 identical subunits (vertices) which
contain identical asymmetric protomers arranged as 12 pentamers.

• Each protomer is made up of one copy of four proteins, named VP1,

VP2, VP3 and VP4.

• VP1, VP2 & VP3 are on the virion surface, with VP4 being internal.

• In many picornaviruses there is a deep cleft (approximately 2 nm deep),

often referred to as canyons around each of the 12 vertices of the
icosahedron. These clefts contain the virus attachment sites.
REPLICATION
 REPLICATION

Begins with attachment to a specific cellular receptor ((PVR; CD155;

ICAM-1) expressed on epithelial cells, fibroblasts, and endothelial cells.

Virus is internalized by endocytosis

Genome released by acidic conditions in the endosome

Viruse replicates in the cytoplasm

genome binds directly to ribosomes where it functions as mRNA

 REPLICATION

• Viral polyprotein is synthesized and cleaved into viral

products
• negative strand template is produced by viral RNA
polymerase
• These templates then generate new plus stranded RNA
• Structural protein component assemble, then genome is
inserted to complete maturation
• Virions are released by cell lysis
 ENTEROVIRUSES
• most enteroviruses are cytolytic

• they cause direct damage to the cell by preventing cellular

mRNA from binding to the ribosomes

• also viral mRNA competes with cellular mRNA for ribosomal

binding sites

• symptoms vary with the tissue trophism of the enterovirus

• most enteroviruses cause viremia

ENTEROVIRUSES
 ENTEROVIRUSES

• Replicate mainly in the gut.

• Unlike rhinoviruses, they are stable in acid pH
• 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))
 POLIOVIRUS

• 3 serotypes of poliovirus (1, 2, and 3) 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.
 TRANSMISSION

Fecal – oral route: poor hygiene, dirty diapers (especially

in day-care settings)

Ingestion via contaminated food and water

Contact with infected hands

Inhalation of infectious aerosols

 PATHOGENESIS

• Fecal/oral route of entry

• The incubation period is usually 7 - 14 days.
• Virus multiplies in the oropharyngeal and intestinal mucosa.
• The lymphatic system are invaded and the virus enters the blood resulting
in a transient viraemia.
• In a minority of cases, virus pass through blood brain barrier and Infects
anterior horn cells of motor neurons in spinal cord causing flaccid
paralysis’
• Virus shed in feces
 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%) –

• Paralytic polio is generally as a result of lower motor neuron damage and
leading to a flaccid paralysis of the lower extremity
• Bulbar polio – causes damage to the respiratory centers in the medulla
Child with polio sequelae
 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.
 PREVENTION

• No specific antiviral therapy is available. However the

disease may be prevented through vaccination. There
are two vaccines available.
• Oral Polio vaccine (OPV live, attenuated, Sabin, 1957)
• Inactivated Poliovirus vaccine (IPV, Salk, 1954)
• Both killed-virus and live-virus vaccines induce
antibodies and protect the central nervous system from
subsequent invasion by wild virus.
 ADVANTAGES AND DISADVANTAGES OF OPV

Advantages
• Effectiveness
• Lifelong immunity
• Induction of secretory antibody response similar to that of natural
infection
• Possibility of attenuated virus circulating in community by spread to
contacts (indirect immunization)(herd immunity)
• Ease of administration
• Lack of need for repeated boosters
 ADVANTAGES AND DISADVANTAGES OF OPV

• Disadvantages
• Risk of vaccine-associated poliomyelites in
vaccine recipients or contacts
• Spread of vaccine to contacts without their
consent
• Unsafe administration for immunodeficient
patients
 ADVANTAGES AND DISADVANTAGES OF IPV

Advantages
• Effectiveness
• Good stability during transport and in storage
• Safe administration in immunodeficient patients
• No risk of vaccine-related disease
 ADVANTAGES AND DISADVANTAGES OF IPV

Disadvantages
• Lack of induction of local (gut) immunity
• Need for booster vaccine for lifelong immunity
• Fact that injection is more painful than oral administration
• Fact that higher community immunization levels are
needed than with live vaccine
 RHINOVIRUSES

• bind to ICAM-1 receptors on respiratory epithelial

cells
• produce a slow cytolytic effect; not via cellular m-
RNA mechanism
• temperature and pH restrict viruses to the upper
respiratory tract
• no viremia occurs in Rhinovirus infections
 RHINOVIRUS

• Most frequent cause of the common cold.

• Produce localized infection of the nose .

• Each serotype (>115) is distinct.

• More heat and acid labile than the enteroviruses.

• Symptoms occur 2 to 4 days after exposure and last about one week.

• Transmission is by contact with respiratory secretions (e.g. air,

hands, door handles, inanimate objects)
 CLINICAL DISEASE

• Cause Acute Rhinitis or Common Cold

• nasal obstruction accompanied by sneezing,
rhinorrhea (runny nose), mild pharyngitis, headache,
and malaise
• without secondary bacterial infection, rhinovirus
infections seldom are accompanied by fever
 HOST DEFENSES

• virally infected cells secrete interferon which limits the

progression of infection

• Nasal secretory IgA, and serum IgG also contribute to recovery,

but produce minimal long term protection due to serotype
variation (type specific immunity)

• cell-mediated immunity plays very little role in controlling

rhinoviruses
 DIAGNOSIS
• mostly based upon symptoms
• serology
• no antigen in common with all Rhinoviruses
• must find antibody to specific serotype
• Culture human diploid fibroblasts at 33 C
 COXSACKIEVIRUSES
• They are classified as coxsackievirus group A (A1 to A24)
and
• coxsackievirus group B (B1 to B6)

• Disesases caused by B serotypes in humans include

aseptic meningitis and
respiratory and undifferentiated febrile illnesses.
Herpangina (vesicular pharyngitis),
hand-foot-and-mouth disease, and
acute hemorrhagic conjunctivitis
 COXSACKIEVIRUSES

• Disesases caused by B serotypes include:

• pleurodynia (epidemic myalgia),
• myocarditis,
• pericarditis,

• A number of group A and B serotypes can give rise to

meningoencephalitis and paralysis.
 ECHOVIRUSES

• There are 32 echoviruses (types 1-34; echovirus 10 and 28 were found

to be other viruses and thus the numbers are unused).

• Echoviruses are associated with various disorders including

• respiratory illnesses,
• febrile illnesses with or without rash,
• Boston exanthema,
• aseptic meningitis,
• paralytic diseases,
• and occasional conjunctivitis