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Picornaviruses

Picornaviruses. Chapter 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

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Picornaviruses

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  1. Picornaviruses • Chapter 36

  2. 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

  3. Properties • Classification • Family Picornaviridae • Genera • Enterovirus • Rhinovirus • Hepatovirus • Parechovirus • Aphthovirus • Cardiovirus

  4. 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 proteaseactivity 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Coxsakieviruses • 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

  10. 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

  11. 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

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