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What else can we do for important EV71 issues ?

What else can we do for important EV71 issues ?. Speaker: 黃思偉. Enterovirus 71 (EV71). 1. Picornaviridae family Non-enveloped (+) ssRNA virus 2. Mild symptoms without CNS infection: Hand, foot and mouth disease (HFMD) Herpangina 3. CNS infection and complication:

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What else can we do for important EV71 issues ?

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  1. What else can we do for important EV71 issues ? Speaker: 黃思偉

  2. Enterovirus 71 (EV71) 1. Picornaviridae family Non-enveloped (+) ssRNA virus 2. Mild symptoms without CNS infection: Hand, foot and mouth disease (HFMD) Herpangina 3. CNS infection and complication: Brainstem encephalitis Aseptic meningitis Polio-like syndrome Neurogenic pulmonary edema (NPE) http://www.infektionsnetz.html

  3. Unresolved important issues • Molecular neurovirulence determinant • Neuron-tropism determinant (receptor, viral factor or host factor-dependent) • Neuron-invasion from peripheral to CNS • Pulmonary edema (PE) generating after EV71-caused CNS damage • How milrinone alleviates EV71-induced PE • Receptor-dependent infection or not, and what is the receptor ? • The generation of highly pathogenic EV71, intertypic recombination?

  4. MP4, a mouse adapted EV71 strain, caused neurological disease and death in mice after oral infection Wang YF et al. Journal of Virology 78: 7916-24 (2004) Day post inoculation

  5. EV71 EV71

  6. The inoculation route determines disease progress

  7. In PBMC The p.o. inoculation results in viremia early without severe neuroinvasion

  8. The i.m. inoculation site where nearer to CNS has faster neuroinvasion and viral titers

  9. Colchicine reduces EV71 spread from hindlimb to CNS in a dose-dependent manner Colchicine: exonal transport blocking agent

  10. EV71 induces BBB permeability after 30 hr post inoculation

  11. http://www.gsbs.utmb.edu/ A retrograde axonal transmission from gastrointestinal tract to CNS in EV71 infection Muscle/nerve termini or viremia Gastrointestinal tract ?

  12. Parental strain EV71/4643 is neurovirulent but not neuroinvasive from intestine to CNS.

  13. EV71/4643 versus EV71/MP4 • Different replication rate in vitro or in vivo in the gastrointestinal tract (GI tract): host factor or virus factor effect? • Different infection frequency in GI tract, receptor-associated binding? • Molecular difference-associated viral replication determinants: IRES or other non-structure proteins • Vehicle-dependent transmission to nerve termini: M cell? Capillary? Lymphoid system?

  14. i.c. inoculation Chen CS et al. Journal of Virology (2007)

  15. Neurogenic pulmonary edema Acta Anaesthesiol Scand51: 447–455 (2007)

  16. Wang SM et al. The Journal of Infectious Diseases 188:564–70 (2003)

  17. IL-6 CNS involvement coupled with systemic inflammation may trigger EV71-induced PE WBC Glucose Clinical Infectious Diseases 36: 269–274 (2003)

  18. IL-13 Milrinone (+) Milrinone (-) Milrinone reduces mortality, vital signs, and inflammation cytokine in patients with EV71-induced PE

  19. Serum levels of IL-6, IL,-10 and IFN-g elevated after day 3 in EV71-infected mice Serum Lung Brain

  20. Brainstem injury by EV71 In EV71-infection, if sufficient amount of proinflammatory cytokines following brainstem encephalitis can develop PE.

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