Monday, June 3, 2013

POLIO

POLIO
Clinics and programs to global eradikasi

Taxonomy Enterovirus
1. Enterovirus 71 serotypes, is multiplying particularly in colon
2. Fam. Pico-rna-viridae
3. Clinical manifestations vary widely
    - Asymptomatic until ARI
    - Aseptic meningitis
    - Miokarditis
    - Encephalitis
    - Paralytic poliomyelitis.
4. Each clinic symptoms overlap each other and serotypes are not typical
    for the serotypes

Human Enterovirus
Subklasifikasi Fam. Picornaviridae (human pathogen)
I.    Human enterovirus
      Poliovirus ------------: serotipe 1,2,3
      Echovirus-------------:  serotipe 1-9, 11-27,29-34
      Coxsackie virus A----:  serotipe 1-22,24
      Coxsackie virus B----:  serotipe 1-6
      Enterovirus  ---------: serotipe 68-71
 II. Rhinovirus  -----------: rhinovirus 1-100
III. Hepatovirus  ---------: hepatitis A 
Disease of Development
  • Earliest record of polio from Egypt
  • No major outbreaks until the 20th century
  • Advent of modern pluming caused large polio endemics.
 Poliovirus
  • 3 poliovirus serotypes (1, 2, 3) without common antigens.
  • Identical physically, but only 36-52% nucleotide homologus.
  • Humans are the only host
  • Globally dispersed Polioviruses, almost 100% of the population in developing countries exposed before the age of 5.
  • Genome: Single-stranded RNA of positive polarity.
  • Icosohedral, non-enveloped capsid.
  • Canyons on virion surface serve as attachment sites for poliovirus receptor.
  • Family Picornaviridae-meaning small.
- Enterovirus-infecting the gastrointestinal tract.

Detection
  • Reverse transcriptase PCR is the only reliable method
  • Super stable virus (>500 days in tap water)
  • Neutralized when heated to 50C for 30 minutes
  • Stable at pH of 3.0 to 5.0 for 3 hours
  • Isoelectric point is ~7.0
  • Chlorine inactivates at 0.1ppm (pure virus solution)
  • Iodine also inactivates
 Generalized Path of Invasion
  1. Oral Ingestion (of fecal matter somehow).
  2. Virus multiplies in alimentary mucosa; tonsils and Peyer’s patches early on.
  3. Proceeds into deep cervical and mesenteric lymph nodes, then into bloodstream.
  4. Enters CNS through either BBB or via Peripheral Nerves. (Sciatic)
  5. Replicates in motor neurons of CNS.

   Poliovirus life-cycle

Receptor-Mediated Endocytosis
1. PVR-Poliovirus Receptor
  • Member of Immunoglobin (Ig) Superfamily
  • 3 Ig domains or “loops.” Polio binds to extracellular domain, followed by a membrane spanning domain and a cytoplasmic domain.
  • + PVR binds to “canyon” in Polio capsid
  • 2 functional PVR’s (hPVR in human); PVR alpha and gamma, which differ in placement of epithelial polarized cells. 
 2     Poliovirus binds to PVR at a “canyon” site on the virus surface,
      and the virus-receptor complex is taken into the cell by endocytosis.
      - Results in a conformational change in the virus’s capsid, which leads to uncoating.


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