Enteroviruses

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Enteroviruses are picornaviruses.Other picornaviruses include:rhinoviruses (115 serotypes)cardiovirusesapthoviruses (foot and mouth disease of cattle, sheep)hepatoviruses

Types

S.T.A.R.

m

Cocksackie

A

B

Echo

Polio

Other

Polio

Characteristics

Pathophysiology

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Polioviral replication in tonsil and intestinal epithelial cells, lymphoid tissueInfection of draining lymph nodesPrimary viremiaSeeding of reticuloendothelial organs and target organ (CNS in polio)Viral infection of cells =>lytic deathSome symptoms may be caused by host immune response to tissue injuryMolecular mimicry: virus-induced autoimmune response

Clinical

Post-polio syndrome

30-40 years after acute

Symptoms

ALS-like

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Joint painFatigueDifficulty swallowingWeakness in certain muscle groupsDecreased endurance

Non life-threatening

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Unlike ALS

Paralytic polio

Fever

Malaise

Head ache

Stiff neck

Meningitis-like symptoms

Infantile paralysis (possible)

Diagnosis

Tissue culture

Serology

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4-fold Ab increase

PCR

Kits

Epidemiology

Paradox

Children w/ poor hygiene & sanitation

Improved sanitation correlated with increased epidemics

Exposure postponed to older children, adults

Disease more severe

Incubation period

2-10 days

99% asymptomatic

1% paralysis, death from resp. failure

Prevention

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Complete Eradication?Virulent poliovirus "replaced" with attenuated strain; risk of VAPP (vaccine-associated paralytic polio)Still endemic in developing countriesGoal to eradicate worldwide within decadeHard to justify cost ($250 million per year) when few children get itMust be cooperative effort worldwideDelays will lessen urgencyTotal eradication needed before vaccination can safely be stopped, otherwise further epidemics possible

Vaccines

Killed Salk

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Preferred

No viral replication

Safe for immunodeficient

Induces humoral immunity

Live Sabin

Confers intestinal immunity (IgM)

Economical, stable, administered in field

Spread to other house members

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Can be good or bad

Poliomyelitis

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Some risk of contracting mutated virusCDC panel now advises return to Salk vaccine

Treatment

Post-polio

No specific AV

General

Characteristics

Structure

Molecular

VP1-4 capsid proteins

VPg protein

5' end

Viral encoded RNA polymerase

Infectious mRNA to polyprotein P1

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Untranslated regions at both termini1st third of polyprotein is P1 (capsid)No easy way to summarize:Multiplication mechanism:Attachment via VP1 to specific host cell surface receptorsGenome immediately translated to yield polyproteinFirst 1/3 of polyprotein is P1 (capsid), remainder (P2, P3) for replicationP1 cleaved into VP0, VP1, VP3 with viral proteaseVP0 cleaved to VP2 and VP4 =>maturation and infectivityRNA-directed RNA polymerase makes (-) strand intermediate, template for genome copiesCapsid assembly, genome insertionProtease (protein 2A) cleaves host cap binding protein complex => host shutoffExits host cells by lysis

Small

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PicornaviridaePico for small

Icosahedral

Infection time course

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Infection time course1-2 h: host shutoff2.5-3 h: viral protein synthesis, vacuolation of cytoplasm\3-4 h: permeabilization of host plasma membrane4-6 h: virus assembly6-10 h: virus release

General properties

GI tract

Grow at 37 degrees

Shed in feces

Cultured in primates

67 serotypes

Resistant

Low pH

Common disinfectants

Sensitive

Hypochlorite

Formaldehyde

Clinical

Cocksacievirus B

CNS

Viral meningitis

Encephalitis

Cardio

Myocarditis

Pericarditis

Pleurodynia

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Bornholm disease"Devil's Grip"

Polio-like paralysis

Pancreatic (diabetes) and resp. infections

Cocksackievirus A

Hand-foot-and-mouth disease

Cold-like symptoms

Blister-like rash on hands, feet

Self-limiting

Herpangina

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Herpangina: an infectious disease, esp. of children, characterized by a sudden occurrence of fever, loss of appetite, and throat ulcerations, caused by a Coxsackie virus.

Enterovirus 72

Hepatitis A disease

Echovirus, Coxsackie A21 or A24

Rhinovirus-like "colds"

Poliovirus

Polio

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Eradicated in U.S.

Post-polio syndrome

Epidemiology

Transmission

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What route?What is the reservoir?

Fecal-oral

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Contaminated water

Human host needed

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No known animal reservoirs

Place

Widespread

DCC

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DCC = Day care centers

Person

Common in children

Time

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Seasonality?

Temperate

Summer, autumn

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Due to water exposure

Tropical

Year-round

Treatment

Coxsackievirus infection

Self-limiting

Pleconaril

Not FDA-approved

Blocks uncoating step