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
