PicornavirusesChapter 36

Properties

• Structure and composition

• 30 nm, icosahedral

• plus-strand RNA, 7.2-8.4 kb• RNA is polyadenylated

• Ten genes, eleven proteins (poliovirus) • VP1, VP2, VP3, VP4 structural proteins

• VP4 interacts with viral RNA

• 2A, 2B, 2C proteases

• 3A, 3B, 3C, 3D RNA replication

• Nonenveloped

• Cytoplasmic replication

Properties

• Classification

• Family Picornaviridae

• Genera• Enterovirus

• Rhinovirus

• Hepatovirus

• Parechovirus

• Aphthovirus

• Cardiovirus

Replication Overview• Replication is cytoplasmic (poliovirus)

• Attachment to poliovirus receptor (PVR; CD155)

• Internalization by receptor-mediated endocytosis• Binding to PVR destabilizes poliovirus’ structure

• RNA released into cytoplasm• 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

Pathogenesis of Polio• Poliovirus

• Principally an infection of the gastrointestinal tract• Before the vaccine, swimming pools were often closed during poliovirus

outbreaks

• Clinical spectrum

• Abortive poliomyelitis• Most common

• Fever, malaise, headache, vomiting, etc.

• Resolves in about a week

• Nonparalytic poliomyelitis (an aseptic meningitis)• Similar symptoms, but also back pain

• Paralysis can occur in a small percentage of cases

• Paralytic poliomyelitis• Motor neuron damage

• Mostly flaccid paralysis, but spasms in some

• Recovery within 6 months, otherwise permanent

• Progressive postpoliomyelitis muscle atrophy (postpolio syndrome)• Can appear decades after polio infection

• Not caused by viral recrudescence, but probably because of previous damage

Polio• 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

Polio• Prevention and control

• Vaccination is the principal means

• Two vaccines available

• Salk - inactivated, percutaneous inoculation (IPV)

• Sabin - live attenuated trivalent, oral administration (OPV)• 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

Coxsakieviruses• Properties

• Two groups; A and B

• 29 serotypes

• Newborn mice are highly susceptible

• Pathogenesis

• Neurologic• An aseptic meningitis

• A7 and A9 most common causes

• Polio-like, but paralysis is rare

• Full recovery

• Skin and mucosa• Herpangina (severe pharyngitis)

• A2-A6, 8, 10 most common

• Hand-foot-and-mouth disease

• Blisters on tissues

• Usually A16

• Resolves without complications

• Pathogenesis (cont.)

• Cardiac and muscular (Group B)

• Pleurodynia• Chest pains, 1-2 weeks

• Self resolving

• Myocarditis• Inflammation of the heart

• Can be fatal in newborns

• Survivors can have permanent heart damage

• Others• Acute hemorrhagic conjunctivitis

• Respiratory infections (“colds”)

• GI infections

• Diabetes?

• Laboratory diagnosis• Virus isolation

• Serology

• PCR

Coxsakieviruses

Echoviruses/Rhinoviruses

• 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

Foot and Mouth Disease

• 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