HIV-1 gp120 proteins alter tight junction protein expression and brain endothelial cell permeability: Implications for the pathogenesis of HIV-associated dementia

Georgette D. Kanmogne, Charles Primeaux, Paula Grammas

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Breakdown of the blood-brain barrier (BBB) is commonly seen in patients with HIV-associated dementia (HAD) despite the lack of productive infection of the brain endothelium. It is likely that secreted viral products play a major role in BBB damage and the development of HAD. The objective of this study is to determine the effects of gp120 proteins on brain endothelial cell permeability and junctional protein expression. Our results showed that treatment of cultured human brain endothelial cells with gp120 for 24 hours results in increased permeability of the endothelial monolayer. Also, gp120 proteins caused disruption and downregulation of the tight junction proteins ZO-1, ZO-2, and occludin in these cells. Other junctional proteins such as claudin-1 and claudin-5 were unaffected by gp120 treatment. These data demonstrate that HIV gp120 proteins alter both the functional and molecular properties of the BBB, which could increase trafficking of HIV, infected cells, and toxic humoral factors into the central nervous system and contribute to the pathogenesis of HAD.

Original languageEnglish (US)
Pages (from-to)498-505
Number of pages8
JournalJournal of Neuropathology and Experimental Neurology
Volume64
Issue number6
DOIs
StatePublished - Jun 2005

Fingerprint

AIDS Dementia Complex
Tight Junction Proteins
HIV-1
Permeability
Endothelial Cells
Blood-Brain Barrier
Brain
Proteins
Claudin-5
Zonula Occludens-1 Protein
Claudin-1
Occludin
Human Immunodeficiency Virus Proteins
Poisons
Endothelium
Down-Regulation
Central Nervous System
HIV
Therapeutics
Infection

Keywords

  • HIV-gp120
  • Human brain endothelial cells
  • Tight junction proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

@article{910f16ead02d43a3a59a18f89387d97a,
title = "HIV-1 gp120 proteins alter tight junction protein expression and brain endothelial cell permeability: Implications for the pathogenesis of HIV-associated dementia",
abstract = "Breakdown of the blood-brain barrier (BBB) is commonly seen in patients with HIV-associated dementia (HAD) despite the lack of productive infection of the brain endothelium. It is likely that secreted viral products play a major role in BBB damage and the development of HAD. The objective of this study is to determine the effects of gp120 proteins on brain endothelial cell permeability and junctional protein expression. Our results showed that treatment of cultured human brain endothelial cells with gp120 for 24 hours results in increased permeability of the endothelial monolayer. Also, gp120 proteins caused disruption and downregulation of the tight junction proteins ZO-1, ZO-2, and occludin in these cells. Other junctional proteins such as claudin-1 and claudin-5 were unaffected by gp120 treatment. These data demonstrate that HIV gp120 proteins alter both the functional and molecular properties of the BBB, which could increase trafficking of HIV, infected cells, and toxic humoral factors into the central nervous system and contribute to the pathogenesis of HAD.",
keywords = "HIV-gp120, Human brain endothelial cells, Tight junction proteins",
author = "Kanmogne, {Georgette D.} and Charles Primeaux and Paula Grammas",
year = "2005",
month = "6",
doi = "10.1093/jnen/64.6.498",
language = "English (US)",
volume = "64",
pages = "498--505",
journal = "Journal of Neuropathology and Experimental Neurology",
issn = "0022-3069",
number = "6",

}

TY - JOUR

T1 - HIV-1 gp120 proteins alter tight junction protein expression and brain endothelial cell permeability

T2 - Implications for the pathogenesis of HIV-associated dementia

AU - Kanmogne, Georgette D.

AU - Primeaux, Charles

AU - Grammas, Paula

PY - 2005/6

Y1 - 2005/6

N2 - Breakdown of the blood-brain barrier (BBB) is commonly seen in patients with HIV-associated dementia (HAD) despite the lack of productive infection of the brain endothelium. It is likely that secreted viral products play a major role in BBB damage and the development of HAD. The objective of this study is to determine the effects of gp120 proteins on brain endothelial cell permeability and junctional protein expression. Our results showed that treatment of cultured human brain endothelial cells with gp120 for 24 hours results in increased permeability of the endothelial monolayer. Also, gp120 proteins caused disruption and downregulation of the tight junction proteins ZO-1, ZO-2, and occludin in these cells. Other junctional proteins such as claudin-1 and claudin-5 were unaffected by gp120 treatment. These data demonstrate that HIV gp120 proteins alter both the functional and molecular properties of the BBB, which could increase trafficking of HIV, infected cells, and toxic humoral factors into the central nervous system and contribute to the pathogenesis of HAD.

AB - Breakdown of the blood-brain barrier (BBB) is commonly seen in patients with HIV-associated dementia (HAD) despite the lack of productive infection of the brain endothelium. It is likely that secreted viral products play a major role in BBB damage and the development of HAD. The objective of this study is to determine the effects of gp120 proteins on brain endothelial cell permeability and junctional protein expression. Our results showed that treatment of cultured human brain endothelial cells with gp120 for 24 hours results in increased permeability of the endothelial monolayer. Also, gp120 proteins caused disruption and downregulation of the tight junction proteins ZO-1, ZO-2, and occludin in these cells. Other junctional proteins such as claudin-1 and claudin-5 were unaffected by gp120 treatment. These data demonstrate that HIV gp120 proteins alter both the functional and molecular properties of the BBB, which could increase trafficking of HIV, infected cells, and toxic humoral factors into the central nervous system and contribute to the pathogenesis of HAD.

KW - HIV-gp120

KW - Human brain endothelial cells

KW - Tight junction proteins

UR - http://www.scopus.com/inward/record.url?scp=20344384260&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20344384260&partnerID=8YFLogxK

U2 - 10.1093/jnen/64.6.498

DO - 10.1093/jnen/64.6.498

M3 - Article

C2 - 15977641

AN - SCOPUS:20344384260

VL - 64

SP - 498

EP - 505

JO - Journal of Neuropathology and Experimental Neurology

JF - Journal of Neuropathology and Experimental Neurology

SN - 0022-3069

IS - 6

ER -