User:Hansene/MicroQEWUSTL paper2

Toll-like receptor 3 mediates West Nile Virus entry into the brain causing lethal encephalitis

Wang, et al

category: virology

Main Points: understand the role of TLR3 in CNS viral (WNV) infections

Experimental designs/model organism KO mice TLR3-/- (also used TNFRSF1a-/- and IL6-/- mice) poly(I:C) is a synthetic TLR3 ligand (looks like viral RNA)

Figures:

1. TLR3-/- mice have better survival (40%) than WT (who all die) after peritoneal infection.

2. TLR3-/- mice have increased viral load, decreased cytokines in blood.

3. TLR3-/- mice have decreased viral load, decreased cytokines in brain.

4. TLR3-/- mice have decreased inflammation in brain and decreased neural damage (dec. leukocytes, dec. monocytes).

5. BBB permeability is increased in WNV infected WT mice and in poly(I:C) injected WT mice, but not in TLR3-/- mice.

6. TLR3-mediated disruption of BBB is affected by TNFalpha receptor signalling, but IL-6 was not shown to be involved.

Future Directions: 1. safety and efficacy of TLR3 and/or TNF signalling inhibitor 2. explore TLR signalling cascade and its role in CNS infections with other pathogens

Special Note: Michael Diamond and Robyn Klein (both WU profs) wrote a comment on this article.

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