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Poliomyelitis

Harish Jairam
10-13-2003

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
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

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

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

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
TNF 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 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
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
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
Type 3 polio

9% (Eliminated)
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
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
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
Brazils 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

World Polio Map

World Polio Map

World Polio Map

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