Lymphocyte migration through the blood brain barrier (BBB) in feline immunodeficiency virus infection is significantly influenced by the pre-existence of virus and TNF-α within the CNS: studies using an in vitro feline BBB model

Fletcher, N.F., Bexiga, M.G., Brayden, D.J., Brankin, B., Willett, B.J. , Hosie, M.J. , Jacque, J.M. and Callanan, J.J. (2009) Lymphocyte migration through the blood brain barrier (BBB) in feline immunodeficiency virus infection is significantly influenced by the pre-existence of virus and TNF-α within the CNS: studies using an in vitro feline BBB model. Neuropathology and Applied Neurobiology, 35(6), pp. 592-602. (doi: 10.1111/j.1365-2990.2009.01031.x)

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Publisher's URL: http://dx.doi.org/10.1111/j.1365-2990.2009.01031.x

Abstract

<b>Aims</b>: In HIV infection, macrophage-tropic and lymphotropic viruses exist in the host. Central nervous system (CNS) infection is an early and ongoing event, important to understand when developing strategies to treat infection. Some knowledge exists on macrophage-tropic virus interactions with the blood-brain barrier (BBB), and the aim of this study was to investigate lymphotropic lentivirus interactions with the BBB. <b>Methods</b>: Interactions of the lymphotropic feline immunodeficiency virus (FIV) with an <i>in vitro</i> model of the feline BBB were evaluated in scenarios to mimic <i>in vivo</i> infections. <b>Results</b>: Cell-free FIV crossed the BBB in very low quantities, and in the presence of TNF-[alpha], BBB integrity was unaffected. However, cell-associated FIV readily crossed the BBB, but BBB integrity was not significantly altered. Transmigration of uninfected and infected lymphocytes increased in response to TNF-[alpha], accompanied by a moderate disruption of barrier integrity and an up-regulation of VCAM-1 rather than ICAM-1. Significant enhancement of migration and disruption of BBB tight junctions occurred when infected cells and TNF-[alpha] were added to the brain side of the BBB and this enhancement was not mediated through additional TNF-[alpha] production. <b>Conclusions</b>: Small quantities of virus in the brain together with TNF-[alpha] have the potential to stimulate greater cell and viral entry into the CNS and this is likely to involve important factors other than further TNF-[alpha] production. Lymphotropic lentivirus entry to the CNS is governed by many factors similar to macrophage-tropic strains.

Item Type:Articles
Keywords:Blood-brain barrier, lymphocyte, FIV
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hosie, Professor Margaret and Willett, Professor Brian
Authors: Fletcher, N.F., Bexiga, M.G., Brayden, D.J., Brankin, B., Willett, B.J., Hosie, M.J., Jacque, J.M., and Callanan, J.J.
Subjects:Q Science > QR Microbiology > QR355 Virology
S Agriculture > SF Animal culture > SF600 Veterinary Medicine
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Neuropathology and Applied Neurobiology
Publisher:Wiley-Blackwell Publishing
ISSN:0305-1846
ISSN (Online):1365-2990
Published Online:26 May 2009
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
363381Rational Design of a Lentiviral VaccineMargaret HosieMedical Research Council (MRC)G0300387Centre for Virus Research