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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
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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
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.
TJs Astrocyte Blood Vessel (Made from Endothelial Cells) The Blood-Brain Barrier
Transwell Top Chamber Plate Bottom Chamber Assembly of the Blood Brain Barrier Model Fletcher et al (2005) Vet Immuno Immunopathol
EndothelialCells Astrocytes Assembly of the Blood Brain Barrier Model Top Chamber (Blood) Bottom Chamber (Brain)
FIV-infected T cells Top Chamber (Blood) EndothelialCells Astrocytes Bottom Chamber (Brain)
Top Chamber (Blood) EndothelialCells Astrocytes Bottom Chamber (Brain)
Top Chamber (Blood) EndothelialCells Astrocytes Bottom Chamber (Brain)
The effect of cell-free FIV on the feline BBB model Top Chamber (Blood) EndothelialCells Astrocytes Bottom Chamber (Brain)
A: Mya-1 apical B: FIV Mya-1 apical C: Mya-1 apical; TNF basolateral D: FIV Mya-1 apical; TNF basolateral E: Mya-1 apical; TNF apical F: FIV Mya-1 apical; TNF apical G: FIV Mya-1 apical and basolateral H: FIV Mya-1 apical and basolateral; TNF basolateral
**p<0.05 ***p<0.0001 2-tailed Unpaired t test A: Mya-1 apical B: FIV Mya-1 apical C: Mya-1 apical; TNF basolateral D: FIV Mya-1 apical; TNF basolateral E: Mya-1 apical; TNF apical F: FIV Mya-1 apical; TNF apical G: FIV Mya-1 apical and basolateral H: FIV Mya-1 apical and basolateral; TNF basolateral
**p<0.05 2-tailed unpaired t-test • BBB • Mya-1 apical • Mya-1 apical; TNF basolateral • FIV Mya-1 apical; TNF basolateral • Mya-1 apical; TNF apical • FIV Mya-1 apical; TNF apical • FIV Mya-1 apical and basolateral • FIV Mya-1 apical and basolateral; TNF basolateral
Primary Cell Lines Brain endothelial cells Astrocytes Microglia
Histopathological evaluations of tissues from exposure studies