Blood-brain barrier tight junction disruption in human immunodeficiency virus-1 encephalitis

Linda M. Dallasta, Liubomir A. Pisarov, James E. Esplen, Jonette V. Werley, Ashlee Moses, Jay Nelson, Cristian L. Achim

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Abstract

The blood-brain barrier (BBB) plays a critical role in regulating cell trafficking through the central nervous system (CNS) due to several unique anatomical features, including the presence of interendothelial tight junctions that form impermeable seals between the cells. Previous studies have demonstrated BBB perturbations during human immunodeficiency virus encephalitis (HIVE); however, the basis of these permeability changes and its relationship to infiltration of human immunodeficiency virus type 1 (HIV-1)- infected monocytes, a critical event in the pathogenesis of the disease, remains unclear. In this study, we examined CNS tissue from HIV-1- seronegative patients and HIV-1-infected patients, both with and without encephalitis, for alterations in BBB integrity via immunohistochemical analysis of the fight junction membrane proteins, occludin and zonula occludens-1 (ZO-1). Significant tight junction disruption (P <0.001), as demonstrated by fragmentation or absence of immunoreactivity for occludin and ZO-1, was observed within vessels from subcortical white matter, basal ganglia, and, to a lesser extent, cortical gray matter in patients who died with HIVE. These alterations were also associated with accumulation of activated, HIV-1-infected brain macrophages, fibrinogen leakage, and marked astrocytosis. In contrast, no significant changes (P > 0.05) were observed in cerebellar tissue from patients with HIVE compared to HIV-seronegative patients or HIV-1-infected patients without encephalitis. Our findings demonstrate that tight junction disruption is a key feature of HIVE that occurs in regions of histopathological alterations in association with perivascular accumulation of activated HIV-1-infected macrophages, serum protein extravasation, and marked astrocytosis. We propose that disruption of this key BBB structure serves as the main route of HIV-1-infected monocyte entry into the CNS.

Original languageEnglish (US)
Pages (from-to)1915-1927
Number of pages13
JournalAmerican Journal of Pathology
Volume155
Issue number6
StatePublished - Dec 1999

Fingerprint

Tight Junctions
Encephalitis
Blood-Brain Barrier
HIV-1
HIV
Central Nervous System
Monocytes
Occludin
Nerve Tissue
Gliosis
Blood Proteins
Permeability
Membrane Proteins
Macrophages

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Dallasta, L. M., Pisarov, L. A., Esplen, J. E., Werley, J. V., Moses, A., Nelson, J., & Achim, C. L. (1999). Blood-brain barrier tight junction disruption in human immunodeficiency virus-1 encephalitis. American Journal of Pathology, 155(6), 1915-1927.

Blood-brain barrier tight junction disruption in human immunodeficiency virus-1 encephalitis. / Dallasta, Linda M.; Pisarov, Liubomir A.; Esplen, James E.; Werley, Jonette V.; Moses, Ashlee; Nelson, Jay; Achim, Cristian L.

In: American Journal of Pathology, Vol. 155, No. 6, 12.1999, p. 1915-1927.

Research output: Contribution to journalArticle

Dallasta, LM, Pisarov, LA, Esplen, JE, Werley, JV, Moses, A, Nelson, J & Achim, CL 1999, 'Blood-brain barrier tight junction disruption in human immunodeficiency virus-1 encephalitis', American Journal of Pathology, vol. 155, no. 6, pp. 1915-1927.
Dallasta, Linda M. ; Pisarov, Liubomir A. ; Esplen, James E. ; Werley, Jonette V. ; Moses, Ashlee ; Nelson, Jay ; Achim, Cristian L. / Blood-brain barrier tight junction disruption in human immunodeficiency virus-1 encephalitis. In: American Journal of Pathology. 1999 ; Vol. 155, No. 6. pp. 1915-1927.
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