Transcript 09 Chapter 36 Picornaviruses

Picornaviruses
Chapter 36
Properties
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Structure and composition
30 nm, icosahedral
plus-strand RNA, 7.2-8.4 kb
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Ten genes, eleven proteins
(poliovirus)
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RNA is polyadenylated
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VP1, VP2, VP3, VP4 structural proteins
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VP4 interacts with viral RNA
2A, 2B, 2C proteases
3A, 3B, 3C, 3D RNA replication
Nonenveloped
Cytoplasmic replication
Properties
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Classification
Family Picornaviridae
Genera
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Enterovirus
Rhinovirus
Hepatovirus
Parechovirus
Aphthovirus
Cardiovirus
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Replication Overview
Replication is cytoplasmic (poliovirus)
Attachment to poliovirus receptor (PVR; CD155)
Internalization by receptor-mediated endocytosis
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Binding to PVR destabilizes poliovirus’ structure
RNA released into cytoplasm
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It’s unclear how the RNA is released, but evidence suggests that VP4 is
injected into the cytoplasm through the endosome membrane, taking the RNA
with it
The RNA is bound by free ribosomes and a single polypeptide is
synthesized
This polypeptide is termed the polyprotein
It has intrinsic protease activity and undergoes autocleavage
It also cleaves the cellular eIF4G, disabling cellular translation
Viral RNA polymerase synthesizes minus strand RNA, then plus
strand
Virus assembly occurs
When the cell dies, progeny virus is released
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Pathogenesis of Polio
Poliovirus
Principally an infection of the gastrointestinal tract
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Before the vaccine, swimming pools were often closed during poliovirus
outbreaks
Clinical spectrum
Abortive poliomyelitis
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Most common
Fever, malaise, headache, vomiting, etc.
Resolves in about a week
Nonparalytic poliomyelitis (an aseptic meningitis)
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Similar symptoms, but also back pain
Paralysis can occur in a small percentage of cases
Paralytic poliomyelitis
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Motor neuron damage
Mostly flaccid paralysis, but spasms in some
Recovery within 6 months, otherwise permanent
Progressive postpoliomyelitis muscle atrophy (postpolio
syndrome)
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Can appear decades after polio infection
Not caused by viral recrudescence, but probably because of previous
Polio
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Laboratory diagnosis
Cell culture was routinely used
Since polio is not a disease of the West, no new diagnostic
methods have been developed
Immunity
VP1 is principal target of neutralizing antibodies
Provides life-long immunity
Global eradication
Humans are only reservoir
Should be the second infectious disease eradicated
Target of 2009
Epidemiology
Oral-fecal route
Swimming pools
Close contact
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Polio
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Prevention and control
Vaccination is the principal means
Two vaccines available
Salk - inactivated, percutaneous inoculation (IPV)
Sabin - live attenuated trivalent, oral administration (OPV)
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One of the strains has a known propensity for reversion to pathogenicity
Can cause polio in post-vaccination exposures (i.e., not the vaccinated
person)
In nations where polio has been eradicated, children are given
the Salk vaccine
Other nations use the Sabin vaccine
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Coxsakieviruses
Properties
Two groups; A and B
29 serotypes
Newborn mice are highly susceptible
Pathogenesis
Neurologic
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An aseptic meningitis
A7 and A9 most common causes
Polio-like, but paralysis is rare
Full recovery
Skin and mucosa
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Herpangina (severe pharyngitis)
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A2-A6, 8, 10 most common
Hand-foot-and-mouth disease
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Blisters on tissues
Usually A16
Resolves without complications
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Coxsakieviruses
Pathogenesis (cont.)
Cardiac and muscular (Group B)
Pleurodynia
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Chest pains, 1-2 weeks
Self resolving
Myocarditis
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Inflammation of the heart
Can be fatal in newborns
Survivors can have permanent heart damage
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Others
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Acute hemorrhagic conjunctivitis
Respiratory infections (“colds”)
GI infections
Diabetes?
Laboratory diagnosis
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Virus isolation
Serology
PCR
Echoviruses/Rhinoviruses
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Echoviruses
Enteric cytopathogenic human orphan viruses
30+ serotypes
GI and cold-like infections
Rhinoviruses
Common cold viruses
More than 100 serotypes known
Immunity is not cross protective
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Foot and Mouth Disease
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Major problem in domesticated livestock
Highly contagious
Mortality can reach 70%
Immunity is short-lived
Some cattle can remain persistently-infected for months
General response: cull the herds
Not generally found in the United States
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