Cited by 151Barrier Structure and Function StudiesMosquito-borne diseases and controlProtease and Inhibitor Mechanisms

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Reversal of West Nile virus-induced blood–brain barrier disruption and tight junction proteins degradation by matrix metalloproteinases inhibitor

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Verma, Saguna, Kumar, Mukesh, Gurjav, Ulziijargal, Lum, Stephanie, Nerurkar, Vivek R.·2010·Virology

DOI 10.1016/j.virol.2009.10.036PMC PMC3102050

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Abstract

Though compromised blood-brain barrier (BBB) is a pathological hallmark of WNV-associated neurological sequelae, underlying mechanisms are unclear. We characterized the expression of matrix metalloproteinases (MMP) in WNV-infected human brain microvascular endothelial cells (HBMVE) and human brain cortical astrocytes (HBCA), components of BBB and their role in BBB disruption. Expression of multiple MMPs was significantly induced in WNV-infected HBCA cells. Naïve HBMVE cells incubated with the supernatant from WNV-infected HBCA cells demonstrated loss of tight junction proteins, which were rescued in the presence of MMP inhibitor, GM6001. Further, supernatant from WNV-infected HBCA cells compromised the in vitro BBB model integrity. Our data suggest astrocytes as one of the sources of MMP in the brain, which mediates BBB disruption allowing unrestricted entry of immune cells into the brain, thereby contributing to WNV neuropathogenesis. Because of the unavailability of WNV antivirals and vaccines, use of MMP inhibitors as an adjunct therapy to ameliorate WNV disease progression is warranted.

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Authors: Verma, S., Kumar, M., Gurjav, U., Lum, S., & Nerurkar, V. R.
Affiliations: University of Hawaiʻi at Mānoa (US)
Corresponding author: Nerurkar, Vivek R.
ORCID: Verma, Saguna
Kumar, Mukesh
Gurjav, Ulziijargal
Nerurkar, Vivek R.
Venue: Virology
Publisher: Elsevier BV
Published: 2010-02
Volume: 397
Issue: 1
Pages: 130-138
ISSN: 0042-6822 (ISSN-L)
DOI: 10.1016/j.virol.2009.10.036
PMC: PMC3102050
OpenAlex: W1968754528
Cited by: 151
References: 54
Citations by year: 2026: 3 · 2025: 10 · 2024: 14 · 2023: 5 · 2022: 7 · 2021: 13 · 2020: 6 · 2019: 7 · 2018: 7 · 2017: 9 · 2016: 5 · 2015: 15 · 2014: 14 · 2013: 9 · 2012: 16
FWCI: 5.55
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1262 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Virology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Hawaii Community Foundation (20050405)
Research Centers in Minority Institutions Program (G12RR003061)
Centers of Biomedical Research Excellence (P20RR018727)
Topics: Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Keywords: West Nile virus, blood-brain barrier disruption, matrix metalloproteinases, tight junction proteins, astrocytes, brain microvascular endothelial cells, GM6001, matrix metalloproteinase inhibitors, neuroinflammation
MeSH terms: Astrocytes, Blood-Brain Barrier, Dipeptides, Humans, Membrane Proteins, Phosphoproteins, Protease Inhibitors, West Nile virus, Tight Junctions, Matrix Metalloproteinases, Gene Expression Profiling, Endothelial Cells, Matrix Metalloproteinase Inhibitors, Claudin-1, Zonula Occludens-1 Protein

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Reversal of West Nile virus-induced blood–brain barrier disruption and tight junction proteins degradation by matrix metalloproteinases inhibitor

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