A Feline-specific Blood Brain Barrier. Feline Immunodeficiency Virus Lentivirus Natural infection in cats worldwide Induces disease Animal model of HIV.

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Presentation transcript:

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 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< 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< tailed unpaired t-test 1.BBB 2.Mya-1 apical 3.Mya-1 apical; TNF basolateral 4.FIV Mya-1 apical; TNF basolateral 5.Mya-1 apical; TNF apical 6.FIV Mya-1 apical; TNF apical 7.FIV Mya-1 apical and basolateral 8.FIV Mya-1 apical and basolateral; TNF basolateral

Primary Cell Lines Brain endothelial cells Astrocytes Microglia

Histopathological evaluations of tissues from exposure studies