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A Feline-specific Blood Brain Barrier. Feline Immunodeficiency Virus. Lentivirus Natural infection in cats worldwide Induces disease Animal model of HIV infection in man. Feline immunodeficiency virus infection - a model of HIV-1 induced encephalitis. HIV and FIV neurotropic - PowerPoint PPT Presentation
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A Feline-specific Blood Brain Barrier
Feline Immunodeficiency Virus
• Lentivirus• Natural infection in
cats worldwide• Induces disease• Animal model of HIV
infection in man
Feline immunodeficiency virus infection- a model of HIV-1 induced encephalitis
• HIV and FIV neurotropic• Early infection of CNS• Neuroinflammation and degeneration• Limited opportunities to study early infection• Requires well-evaluated animal models
» SIV» FIV
Ryan et al, J Neurovirol 2005
Aims– To investigate the ability of cell-
free & cell-associated FIV to cross the in vitro BBB, and the effect of inflammatory cytokines on this process.
The Blood-Brain Barrier
Blood Vessel(Made from Endothelial Cells)
Astrocyte
TJs
Assembly of the Blood Brain Barrier Model
Plate
Transwell
Bottom Chamber
Top Chamber
Fletcher et al (2005) Vet Immuno Immunopathol
Assembly of the Blood Brain Barrier Model
Top Chamber (Blood)
Bottom Chamber (Brain)
Endothelial Cells
Astrocytes
Top Chamber (Blood)
Bottom Chamber (Brain)
Endothelial Cells
Astrocytes
FIV-infected T
cells
Top Chamber (Blood)
Bottom Chamber (Brain)
Endothelial Cells
Astrocytes
Top Chamber (Blood)
Bottom Chamber (Brain)
Endothelial Cells
Astrocytes
Top Chamber (Blood)
Bottom Chamber (Brain)
Endothelial Cells
Astrocytes
The effect of cell-free FIV on the feline BBB model
A: Mya-1 apicalB: FIV Mya-1 apicalC: Mya-1 apical; TNF basolateralD: FIV Mya-1 apical; TNF basolateralE: Mya-1 apical; TNF apicalF: FIV Mya-1 apical; TNF apicalG: FIV Mya-1 apical and basolateralH: FIV Mya-1 apical and basolateral; TNF
basolateral
Top Chamber (Blood)
Bottom Chamber (Brain)
EndothelialCells
Astrocytes
FIV-infected T cells
**p<0.05
***p<0.0001
2-tailed Unpaired t testA: Mya-1 apicalB: FIV Mya-1 apicalC: Mya-1 apical; TNF basolateralD: FIV Mya-1 apical; TNF basolateralE: Mya-1 apical; TNF apicalF: FIV Mya-1 apical; TNF apicalG: FIV Mya-1 apical and basolateralH: FIV Mya-1 apical and basolateral; TNF basolateral
Transmigration of Mya-1 cellsacross the in vitro BBB
A B C D E F G H0
25
50
75
100Tr
ansm
igra
ted
Mya
-1ce
lls (x
104 )
***
*****
******
Permeability of BBB Models toFD-4 following Mya-1
Transmigration
1 2 3 4 5 6 7 80.0×10 -00
5.0×10 -05
1.0×10 -04
1.5×10 -04
P app
(cm
/s)
**
**p<0.05
2-tailed unpaired t-test1. BBB2. Mya-1 apical3. Mya-1 apical; TNF basolateral4. FIV Mya-1 apical; TNF basolateral5. Mya-1 apical; TNF apical6. FIV Mya-1 apical; TNF apical7. FIV Mya-1 apical and basolateral8. FIV Mya-1 apical and basolateral; TNF basolateral
Primary Cell Lines
Brain endothelial cells
Astrocytes
Microglia
Histopathological evaluations of tissues from exposure studies
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