polio

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Poliomyelitis : 

Poliomyelitis Harish Jairam 10-13-2003

History : 

History Associated with man since ancient times Egyptian hieroglyph indicates presence since 1400 BC 1840 - Heinle characterizes poliomyelitis Poliomyelitis – “grey marrow” in Greek 1954 - Salk vaccine 1960 - Sabin vaccine 1991 – Molla produces polio in vitro from virus RNA 2002 – completele synthetic production

Structure : 

Structure Small; 28 – 30 nm in diameter Structure is intersection of icosahedron and dodecahedron 3 external capsid proteins (VP1, VP2, and VP3) with conserved antiparallel beta barrel cores Capsid structural stability extremely temperature sensitive B – C loop of VP1 important for antigenic site Sequence canyon formed between proteins important for immunological reasons and receptor binding

Structure : 

Structure

Cell Binding and Entry : 

Cell Binding and Entry Binds only to poliovirus receptor (Pvr) Pvr is a transmembrane glycoprotein with three extracellular immunoglobulin like domains Pvr is involved with actin skeleton Poor viral entry probability ( 0.1 - 1%)

Cell Binding and Entry : 

Cell Binding and Entry

Poliovirus Genome : 

Poliovirus Genome Single RNA molecule ~7500 nucleotides 3 sub-regions with 10 protein products IRES important for virulence

Anti-Host Activity : 

Anti-Host Activity Shuts off host transcription 2B, 2BC, and 3A interfere with apoptotic pathways 3A causes tumor necrosis receptor depletion, making cell resistant to TNFα necrosis 2BC, 3A interfere with antiviral cytokine secretion Many transcription factors bound rather than proteolysed Increases cell membrane lipid composition, leads to membrane rupture 5’ UTR determines if the virus will by lytic or nonlytic

RNA Replication : 

RNA Replication RNA polymerase (3D) RNA is copied into –RNA template for further RNA replication; no free -RNA 50:1 ratio +RNA: -RNA Vpg is used as primer for both + RNA synthesis and –RNA synthesis Quality control proteins to maintain only intact RNA is used for replication Mutation prone synthesis, ~1 mutation/ replication

Pathogenesis : 

Pathogenesis Symptoms of poliomyelitis always CNS specific Neurological symptoms found in 1-2% of infected individuals Three possible routes of entry into CNS Retrograde axonal transport Transport across blood – brain barrier Transport via infected macrophages (Trojan Horse) Specific to CD155 (Pvr) receptor Tropic to lower spinal cord and alimentary tract 5’ NTR key to neurovirulence, especially IRES Virus with rhinovirus analogue IRES fails to propagate in neuronal cells Provocation Poliomyelitis

Serotypes : 

Serotypes Specificity to receptor restricts mutation rate; slow genetic drift Occur because of immunological reasons, vary at sequence canyon Three serotypes with no cross immunity Type 1 polio 90% Weakest, only 1% causes neuroparalysis Type 2 polio 9% (Eliminated) Type 3 polio 1% Greater temperature stability Requires trivalent polio vaccine Polioviruses can also vary in phenotype of virulence, host cell lysis, and ability to raise host defense triggers

Vaccines : 

Vaccines Salk or Inactivated Polio Vaccine (IPV) –1954 Formalin killed virus Balance between killing virus and antigenicity (Cutter Incident) Difficult to produce in mass quantities Does not work in tropical climates because of interference from other entric viruses Sabin or Oral Polio Vaccine (OPV) – 1960 Alters IRES function Reduces virus efficiency, replication rate, neuronal invasion Risk of reversion to more virulent form through mutation 1 in 1.2 million vaccinations produces neuronal effects

Eradication : 

Eradication Historically, 0.5% of population became paralyzed by poliomyelitis Easily transmissible, less than 1% clinically recognizable 1988 – World Health Assembly calls for global polio eradication by 2000 Brazil’s innovative immunization campaigns Failures of smallpox eradication campaign Threat of bioterrorism, remaining Laboratory strains, synthetis production Vaccine-driven poliovirus (VDPV) in Egypt, Hispaniola Elimination of Serotype 2

Decline in Poliomyelitis : 

Decline in Poliomyelitis

World Polio Map : 

World Polio Map

World Polio Map : 

World Polio Map

World Polio Map : 

World Polio Map

Resources : 

Resources Semler, Bert L.; Wimmer, Eckard; Molecular Biology of Picornaviruses; ASM Press: Washington, 2002 Koch, Friedrich; Koch, Gehhard; The Molecular Biology of Poliovirus; Springer Verlag: New York, 1985 Semler, Bert L.; Ehrenfeld, Ellie; Molecular Aspects of Picornavirus Infection and Detection; ASM Press: Washington, 1988 Daniel, Thomas M;Robins, Frederick C.; Polio; University of Rochester Press: Rochester, 1997

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